TY  - JOUR
AU  - Divljaković, Jovana
AU  - Milić, Marija
AU  - Namjoshi, Ojas A.
AU  - Tiruveedhula, Veera V.
AU  - Timić, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1931
AB  - The abrupt discontinuation of prolonged benzodiazepine treatment elicits a withdrawal syndrome with increased anxiety as a major symptom. The neural mechanisms underlying benzodiazepine physical dependence are still insufficiently understood. Flumazenil, the non-selective antagonist of the benzodiazepine binding site of GABA(A) receptors was capable of preventing and reversing the increased anxiety during benzodiazepine withdrawal in animals and humans in some, but not all studies. On the other hand, a number of data suggest that GABA(A) receptors containing alpha(1) subunits are critically involved in processes developing during prolonged use of benzodiazepines, such are tolerance to sedative effects, liability to physical dependence and addiction. Hence, we investigated in the elevated plus maze the level of anxiety 24 h following 21 days of diazepam treatment and the influence of flumazenil or a preferential alpha(1)-subunit selective antagonist beta CCt on diazepam withdrawal syndrome in rats. Abrupt cessation of protracted once-daily intraperitoneal administration of 2 mg/kg diazepam induced a withdrawal syndrome, measured by increased anxiety-like behavior in the elevated plus maze 24 h after treatment cessation. Acute challenge with either flumazenil (10 mg/kg) or beta CCt (1.25, 5 and 20 mg/kg) alleviated the diazepam withdrawal-induced anxiety. Moreover, both antagonists induced an anxiolytic-like response close, though not identical, to that seen with acute administration of diazepam. These findings imply that the mechanism by which antagonism at GABA(A) receptors may reverse the withdrawal-induced anxiety involves the alpha(1) subunit and prompt further studies aimed at linking the changes in behavior with possible adaptive changes in subunit expression and function of GABA(A) receptors.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Brain Research Bulletin
T1  - βCCT, an antagonist selective for α1GABAA receptors, reverses diazepam withdrawal-induced anxiety in rats
VL  - 91
SP  - 1
EP  - 7
DO  - 10.1016/j.brainresbull.2012.10.011
ER  - 

@article{
author = "Divljaković, Jovana and Milić, Marija and Namjoshi, Ojas A. and Tiruveedhula, Veera V. and Timić, Tamara and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "The abrupt discontinuation of prolonged benzodiazepine treatment elicits a withdrawal syndrome with increased anxiety as a major symptom. The neural mechanisms underlying benzodiazepine physical dependence are still insufficiently understood. Flumazenil, the non-selective antagonist of the benzodiazepine binding site of GABA(A) receptors was capable of preventing and reversing the increased anxiety during benzodiazepine withdrawal in animals and humans in some, but not all studies. On the other hand, a number of data suggest that GABA(A) receptors containing alpha(1) subunits are critically involved in processes developing during prolonged use of benzodiazepines, such are tolerance to sedative effects, liability to physical dependence and addiction. Hence, we investigated in the elevated plus maze the level of anxiety 24 h following 21 days of diazepam treatment and the influence of flumazenil or a preferential alpha(1)-subunit selective antagonist beta CCt on diazepam withdrawal syndrome in rats. Abrupt cessation of protracted once-daily intraperitoneal administration of 2 mg/kg diazepam induced a withdrawal syndrome, measured by increased anxiety-like behavior in the elevated plus maze 24 h after treatment cessation. Acute challenge with either flumazenil (10 mg/kg) or beta CCt (1.25, 5 and 20 mg/kg) alleviated the diazepam withdrawal-induced anxiety. Moreover, both antagonists induced an anxiolytic-like response close, though not identical, to that seen with acute administration of diazepam. These findings imply that the mechanism by which antagonism at GABA(A) receptors may reverse the withdrawal-induced anxiety involves the alpha(1) subunit and prompt further studies aimed at linking the changes in behavior with possible adaptive changes in subunit expression and function of GABA(A) receptors.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Brain Research Bulletin",
title = "βCCT, an antagonist selective for α1GABAA receptors, reverses diazepam withdrawal-induced anxiety in rats",
volume = "91",
pages = "1-7",
doi = "10.1016/j.brainresbull.2012.10.011"
}

Divljaković, J., Milić, M., Namjoshi, O. A., Tiruveedhula, V. V., Timić, T., Cook, J. M.,& Savić, M.. (2013). βCCT, an antagonist selective for α1GABAA receptors, reverses diazepam withdrawal-induced anxiety in rats. in Brain Research Bulletin
Pergamon-Elsevier Science Ltd, Oxford., 91, 1-7.
https://doi.org/10.1016/j.brainresbull.2012.10.011

Divljaković J, Milić M, Namjoshi OA, Tiruveedhula VV, Timić T, Cook JM, Savić M. βCCT, an antagonist selective for α1GABAA receptors, reverses diazepam withdrawal-induced anxiety in rats. in Brain Research Bulletin. 2013;91:1-7.
doi:10.1016/j.brainresbull.2012.10.011 .

Divljaković, Jovana, Milić, Marija, Namjoshi, Ojas A., Tiruveedhula, Veera V., Timić, Tamara, Cook, James M., Savić, Miroslav, "βCCT, an antagonist selective for α1GABAA receptors, reverses diazepam withdrawal-induced anxiety in rats" in Brain Research Bulletin, 91 (2013):1-7,
https://doi.org/10.1016/j.brainresbull.2012.10.011 . .

TY  - JOUR
AU  - Joksimović, Srđan
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Varagić, Zdravko
AU  - Brajković, Gordana
AU  - Milinković, Marija M.
AU  - Yin, Wenyuan
AU  - Timić, Tamara
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2028
AB  - Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.
T2  - European Neuropsychopharmacology
T1  - Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors
VL  - 23
IS  - 5
SP  - 390
EP  - 399
DO  - 10.1016/j.euroneuro.2012.05.003
ER  - 

@article{
author = "Joksimović, Srđan and Divljaković, Jovana and van Linn, Michael and Varagić, Zdravko and Brajković, Gordana and Milinković, Marija M. and Yin, Wenyuan and Timić, Tamara and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.",
journal = "European Neuropsychopharmacology",
title = "Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors",
volume = "23",
number = "5",
pages = "390-399",
doi = "10.1016/j.euroneuro.2012.05.003"
}

Joksimović, S., Divljaković, J., van Linn, M., Varagić, Z., Brajković, G., Milinković, M. M., Yin, W., Timić, T., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors. in European Neuropsychopharmacology, 23(5), 390-399.
https://doi.org/10.1016/j.euroneuro.2012.05.003

Joksimović S, Divljaković J, van Linn M, Varagić Z, Brajković G, Milinković MM, Yin W, Timić T, Sieghart W, Cook JM, Savić M. Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors. in European Neuropsychopharmacology. 2013;23(5):390-399.
doi:10.1016/j.euroneuro.2012.05.003 .

Joksimović, Srđan, Divljaković, Jovana, van Linn, Michael, Varagić, Zdravko, Brajković, Gordana, Milinković, Marija M., Yin, Wenyuan, Timić, Tamara, Sieghart, Werner, Cook, James M., Savić, Miroslav, "Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors" in European Neuropsychopharmacology, 23, no. 5 (2013):390-399,
https://doi.org/10.1016/j.euroneuro.2012.05.003 . .

TY  - JOUR
AU  - Milić, Marija
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Biawat, Poonam
AU  - Rallapalli, Sundari
AU  - Divljaković, Jovana
AU  - Radulović, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1926
AB  - Inverse agonism at the benzodiazepine site of alpha(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for alpha(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an alpha(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2,5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5,10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1 mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective as GABA(A) inverse agonists.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats
VL  - 241
SP  - 206
EP  - 213
DO  - 10.1016/j.bbr.2012.12.016
ER  - 

@article{
author = "Milić, Marija and Timić, Tamara and Joksimović, Srđan and Biawat, Poonam and Rallapalli, Sundari and Divljaković, Jovana and Radulović, Tamara and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Inverse agonism at the benzodiazepine site of alpha(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for alpha(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an alpha(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2,5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5,10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1 mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective as GABA(A) inverse agonists.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
title = "PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats",
volume = "241",
pages = "206-213",
doi = "10.1016/j.bbr.2012.12.016"
}

Milić, M., Timić, T., Joksimović, S., Biawat, P., Rallapalli, S., Divljaković, J., Radulović, T., Cook, J. M.,& Savić, M.. (2013). PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 241, 206-213.
https://doi.org/10.1016/j.bbr.2012.12.016

Milić M, Timić T, Joksimović S, Biawat P, Rallapalli S, Divljaković J, Radulović T, Cook JM, Savić M. PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. in Behavioural Brain Research. 2013;241:206-213.
doi:10.1016/j.bbr.2012.12.016 .

Milić, Marija, Timić, Tamara, Joksimović, Srđan, Biawat, Poonam, Rallapalli, Sundari, Divljaković, Jovana, Radulović, Tamara, Cook, James M., Savić, Miroslav, "PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats" in Behavioural Brain Research, 241 (2013):206-213,
https://doi.org/10.1016/j.bbr.2012.12.016 . .

TY  - JOUR
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Milić, Marija
AU  - Divljaković, Jovana
AU  - Batinić, Bojan
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1957
AB  - Amnesia is one of the most discussed properties of the benzodiazepine class of drugs. The effects of benzodiazepines on human memory are usually anterograde, while changes in retrograde memory functions were seldom reported. Such inconsistent findings have prompted numerous animal studies investigating the influences of these positive modulators of inhibitory neurotransmission on different stages of memory. Among the benzodiazepines, memory effects of midazolam are of special interest due to its many and varied clinical applications. The present Morris water maze study in adult male Wistar rats was performed in three experiments in which midazolam was administered at doses of 0.5, 1 and 2 mg/kg intraperitoneally, before or immediately after each of five daily learning sessions, with two trials in a session, as well as before the probe test. Midazolam impaired acquisition and subsequent retention of spatial learning of the position of the hidden platform even at a pre-training dose of 0.5 mg/kg. This low dose was not associated with impairment of the procedural component of learning, manifested by increased time spent in the periphery of the pool. The lack of midazolam effect on consolidation has not been confounded by the observed below-chance performance of the control group since our additional experiment using diazepam also administered immediately after each of five learning sessions has revealed a similar pattern of results. Finally, midazolam administered before the probe test impaired retrieval of reference memory at all tested doses. Hence, induction of retrograde, besides anterograde amnesia should be kept in mind as a possibility when midazolam is used in clinical settings.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze
VL  - 241
SP  - 198
EP  - 205
DO  - 10.1016/j.bbr.2012.12.014
ER  - 

@article{
author = "Timić, Tamara and Joksimović, Srđan and Milić, Marija and Divljaković, Jovana and Batinić, Bojan and Savić, Miroslav",
year = "2013",
abstract = "Amnesia is one of the most discussed properties of the benzodiazepine class of drugs. The effects of benzodiazepines on human memory are usually anterograde, while changes in retrograde memory functions were seldom reported. Such inconsistent findings have prompted numerous animal studies investigating the influences of these positive modulators of inhibitory neurotransmission on different stages of memory. Among the benzodiazepines, memory effects of midazolam are of special interest due to its many and varied clinical applications. The present Morris water maze study in adult male Wistar rats was performed in three experiments in which midazolam was administered at doses of 0.5, 1 and 2 mg/kg intraperitoneally, before or immediately after each of five daily learning sessions, with two trials in a session, as well as before the probe test. Midazolam impaired acquisition and subsequent retention of spatial learning of the position of the hidden platform even at a pre-training dose of 0.5 mg/kg. This low dose was not associated with impairment of the procedural component of learning, manifested by increased time spent in the periphery of the pool. The lack of midazolam effect on consolidation has not been confounded by the observed below-chance performance of the control group since our additional experiment using diazepam also administered immediately after each of five learning sessions has revealed a similar pattern of results. Finally, midazolam administered before the probe test impaired retrieval of reference memory at all tested doses. Hence, induction of retrograde, besides anterograde amnesia should be kept in mind as a possibility when midazolam is used in clinical settings.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
title = "Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze",
volume = "241",
pages = "198-205",
doi = "10.1016/j.bbr.2012.12.014"
}

Timić, T., Joksimović, S., Milić, M., Divljaković, J., Batinić, B.,& Savić, M.. (2013). Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 241, 198-205.
https://doi.org/10.1016/j.bbr.2012.12.014

Timić T, Joksimović S, Milić M, Divljaković J, Batinić B, Savić M. Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze. in Behavioural Brain Research. 2013;241:198-205.
doi:10.1016/j.bbr.2012.12.014 .

Timić, Tamara, Joksimović, Srđan, Milić, Marija, Divljaković, Jovana, Batinić, Bojan, Savić, Miroslav, "Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze" in Behavioural Brain Research, 241 (2013):198-205,
https://doi.org/10.1016/j.bbr.2012.12.014 . .

TY  - CONF
AU  - Divljaković, Jovana
AU  - Timić, Tamara
AU  - Milinković, Marija M.
AU  - Batinić, Bojan
AU  - van Linn, Michael
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1661
AB  - Objective : Despite a half century of clinical use and the recognized
potential of benzodiazepine dependence, the mechanisms under-
lying benzodiazepine withdrawal remain insufficiently understood.
The aim of the present study was to assess the influence of the non-
selective antagonist (flumazenil) and the preferential a1-subunit
selective antagonist (bCCt) on the anxiety level after diazepam with-
drawal.
Methods : The male Wistar rats were protractedly treated during
21 days with diazepam (2 mg/kg) or solvent. On the testing day,
24 hours after the last injection, animals from the diazepam-treated
groups received either antagonist (flumazenil or bCCt) or solvent, and
animals from the solvent-treated groups received solvent or diaze-
pam. Twenty minutes after administration of treatment on the testing
day, single animals were placed in the elevated plus maze in order to
assess the level of anxiety.
Results : Two-way ANOVA revealed that animals withdrawn from
diazepam spent significantly less time on the open arms than control
animals (p=0.023). One-way ANOVA, followed by post hoc test, re-
vealed that administration of flumazenil (10 mg/kg) or bCCt (1.25,
5 or 20 mg/kg) reversed the diazepam withdrawal-induced anxiety
(percentage of open arm time : p=0.003, p=0.032, p=0.031 and
p=0.014 compared to the diazepam-withdrawn group, respectively).
Concomitant administration of antagonists (10 mg/kg flumazenil,
or 1.25, 5 or 20 mg/kg bCCt) induced an anxiolytic effect comparable
to that observed after acutely administrated diazepam (percentage of
open arm time : p=0.142, p=0.187, p=0.243 and p=0.290, respect-
ively).
Conclusion : The present study demonstrated that administration
of the a1-selective antagonist bCCt or non-selective antagonist
flumazenil could prevent the withdrawal-induced anxiety and also
induce an anxiolytic-like effect. Moreover, presented results have
suggested that mechanism of preventing the withdrawal-induced
anxiety involves the antagonism at a1-containing GABAA receptors.
PB  - Oxford Univ Press, Oxford
C3  - International Journal of Neuropsychopharmacology
T1  - Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats
VL  - 15
IS  - Supplement 1
SP  - 201
EP  - 201
DO  - 10.1017/S1461145712000508
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1661
ER  - 

@conference{
author = "Divljaković, Jovana and Timić, Tamara and Milinković, Marija M. and Batinić, Bojan and van Linn, Michael and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : Despite a half century of clinical use and the recognized
potential of benzodiazepine dependence, the mechanisms under-
lying benzodiazepine withdrawal remain insufficiently understood.
The aim of the present study was to assess the influence of the non-
selective antagonist (flumazenil) and the preferential a1-subunit
selective antagonist (bCCt) on the anxiety level after diazepam with-
drawal.
Methods : The male Wistar rats were protractedly treated during
21 days with diazepam (2 mg/kg) or solvent. On the testing day,
24 hours after the last injection, animals from the diazepam-treated
groups received either antagonist (flumazenil or bCCt) or solvent, and
animals from the solvent-treated groups received solvent or diaze-
pam. Twenty minutes after administration of treatment on the testing
day, single animals were placed in the elevated plus maze in order to
assess the level of anxiety.
Results : Two-way ANOVA revealed that animals withdrawn from
diazepam spent significantly less time on the open arms than control
animals (p=0.023). One-way ANOVA, followed by post hoc test, re-
vealed that administration of flumazenil (10 mg/kg) or bCCt (1.25,
5 or 20 mg/kg) reversed the diazepam withdrawal-induced anxiety
(percentage of open arm time : p=0.003, p=0.032, p=0.031 and
p=0.014 compared to the diazepam-withdrawn group, respectively).
Concomitant administration of antagonists (10 mg/kg flumazenil,
or 1.25, 5 or 20 mg/kg bCCt) induced an anxiolytic effect comparable
to that observed after acutely administrated diazepam (percentage of
open arm time : p=0.142, p=0.187, p=0.243 and p=0.290, respect-
ively).
Conclusion : The present study demonstrated that administration
of the a1-selective antagonist bCCt or non-selective antagonist
flumazenil could prevent the withdrawal-induced anxiety and also
induce an anxiolytic-like effect. Moreover, presented results have
suggested that mechanism of preventing the withdrawal-induced
anxiety involves the antagonism at a1-containing GABAA receptors.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats",
volume = "15",
number = "Supplement 1",
pages = "201-201",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1661"
}

Divljaković, J., Timić, T., Milinković, M. M., Batinić, B., van Linn, M., Cook, J. M.,& Savić, M.. (2012). Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 15(Supplement 1), 201-201.
https://doi.org/10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1661

Divljaković J, Timić T, Milinković MM, Batinić B, van Linn M, Cook JM, Savić M. Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats. in International Journal of Neuropsychopharmacology. 2012;15(Supplement 1):201-201.
doi:10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1661 .

Divljaković, Jovana, Timić, Tamara, Milinković, Marija M., Batinić, Bojan, van Linn, Michael, Cook, James M., Savić, Miroslav, "Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats" in International Journal of Neuropsychopharmacology, 15, no. Supplement 1 (2012):201-201,
https://doi.org/10.1017/S1461145712000508 .,
https://hdl.handle.net/21.15107/rcub_farfar_1661 .

TY  - CONF
AU  - Milinković, Marija M.
AU  - Timić, Tamara
AU  - Divljaković, Jovana
AU  - Joksimović, Srđan
AU  - Rallapalli, Sundari
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1660
AB  - Objective : The impairing effects of diazepam in Morris water maze
(MWM) could be partially antagonized with co-administration of an
a5 subunit selective antagonist XLi093 (Savic ́ et al., 2009). In order
to further assess the role of the a5GABAA receptors population
in mediating amnesic effects in rats, the present study examined
effects of an a5GABAA selective agonist XLi356 on the MWM
performance.
Methods : Male Wistar rats were given vehicle or 5, 10 and 20 mg/
kg of XLI356 intraperitoneally 20 minutes before the testing. A single-
day water maze task had three swimming blocks, each consisting of
4 trials, lasting a maximum time of 60 s each. Afterwards, a probe trial
was given and a number of standard parameters was calculated.
Additionally, rats were tested in spontaneous locomotor activity
(SLA) and elevated plus maze (EPM) tests, where the sedative and
anxiolytic effects were assessed.
Results : Results were analyzed using one-way ANOVA with post
hoc Student-Newman-Keuls test where applicable. XLi356 signifi-
cantly increased latency to platform (F(3,444)=3.1287, p=0.026) ; post
hoc test revealed that the dose of 20 mg/kg was significantly different
from vehicle. The same dose of XLi356 significantly increased cumu-
lative distance from the platform zone (p=0.028) and the time spent
in the periphery ring (p=0.009), while the path efficiency was on the
control level. On the other hand, XLi356 did not show behavioral
activity in SLA and EPM tests at either of three doses tested.
Conclusion : The present results suggest that ligands with ap-
preciable agonist activity at GABAA receptors containing a5 subunits
may impair memory acquisition in Morris water maze task, without
discernible effects on general behavior. Thus the activity of the ben-
zodiazepine type drugs at a5GABAA receptors should be decreased if
the amnesic effects are to avoid.
PB  - Oxford Univ Press, Oxford
C3  - International Journal of Neuropsychopharmacology
T1  - The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze
VL  - 15
IS  - Supplement 1
SP  - 231
EP  - 231
DO  - 10.1017/S1461145712000508
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1660
ER  - 

@conference{
author = "Milinković, Marija M. and Timić, Tamara and Divljaković, Jovana and Joksimović, Srđan and Rallapalli, Sundari and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : The impairing effects of diazepam in Morris water maze
(MWM) could be partially antagonized with co-administration of an
a5 subunit selective antagonist XLi093 (Savic ́ et al., 2009). In order
to further assess the role of the a5GABAA receptors population
in mediating amnesic effects in rats, the present study examined
effects of an a5GABAA selective agonist XLi356 on the MWM
performance.
Methods : Male Wistar rats were given vehicle or 5, 10 and 20 mg/
kg of XLI356 intraperitoneally 20 minutes before the testing. A single-
day water maze task had three swimming blocks, each consisting of
4 trials, lasting a maximum time of 60 s each. Afterwards, a probe trial
was given and a number of standard parameters was calculated.
Additionally, rats were tested in spontaneous locomotor activity
(SLA) and elevated plus maze (EPM) tests, where the sedative and
anxiolytic effects were assessed.
Results : Results were analyzed using one-way ANOVA with post
hoc Student-Newman-Keuls test where applicable. XLi356 signifi-
cantly increased latency to platform (F(3,444)=3.1287, p=0.026) ; post
hoc test revealed that the dose of 20 mg/kg was significantly different
from vehicle. The same dose of XLi356 significantly increased cumu-
lative distance from the platform zone (p=0.028) and the time spent
in the periphery ring (p=0.009), while the path efficiency was on the
control level. On the other hand, XLi356 did not show behavioral
activity in SLA and EPM tests at either of three doses tested.
Conclusion : The present results suggest that ligands with ap-
preciable agonist activity at GABAA receptors containing a5 subunits
may impair memory acquisition in Morris water maze task, without
discernible effects on general behavior. Thus the activity of the ben-
zodiazepine type drugs at a5GABAA receptors should be decreased if
the amnesic effects are to avoid.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze",
volume = "15",
number = "Supplement 1",
pages = "231-231",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1660"
}

Milinković, M. M., Timić, T., Divljaković, J., Joksimović, S., Rallapalli, S., Cook, J. M.,& Savić, M.. (2012). The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 15(Supplement 1), 231-231.
https://doi.org/10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1660

Milinković MM, Timić T, Divljaković J, Joksimović S, Rallapalli S, Cook JM, Savić M. The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze. in International Journal of Neuropsychopharmacology. 2012;15(Supplement 1):231-231.
doi:10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1660 .

Milinković, Marija M., Timić, Tamara, Divljaković, Jovana, Joksimović, Srđan, Rallapalli, Sundari, Cook, James M., Savić, Miroslav, "The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze" in International Journal of Neuropsychopharmacology, 15, no. Supplement 1 (2012):231-231,
https://doi.org/10.1017/S1461145712000508 .,
https://hdl.handle.net/21.15107/rcub_farfar_1660 .

TY  - CONF
AU  - Timić, Tamara
AU  - Divljaković, Jovana
AU  - Milinković, Marija M.
AU  - Rallapalli, Sundari
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1685
AB  - Objective : It is well known that benzodiazepine binding site ligands
influence learning and memory and that the a5 subunit is significantly
involved in cognition enhancement mediated by the negative modu-
lation of GABAA receptor function. PWZ-029, a moderately selective
a5GABA A receptor inverse agonist, improved learning in passive but
not in active avoidance test, without effects on anxiety or muscle tone.
The aim of this study was to investigate effects of PWZ-029 and
DMCM, a non-selective inverse agonist, on learning ability and short-
term memory in Morris water-maze (MWM) test.
Methods : MWM test was conducted 20 minutes after in-
traperitoneal administration of treatments (solvent, 5, 15 or 30 mg/kg
PWZ-029 or 2 mg/kg DMCM) to male Wistar rats. The single-day
MWM task consisted of 3 consecutive blocks of 4 trials lasting maxi-
mally 60 s each and a probe trial. During spatial learning the platform
was hidden in the middle of the NE quadrant.
Results : Two-way ANOVA with one repeated measure (block) and
animals nested in treatment has shown that latency to find the plat-
form, path efficiency and total distance travelled were on the control
level for DMCM and all doses of PWZ-029. Factors block and treat-
ment were significant only for latency to first entry to the NE quadrant
[block effect : F(2,386)=10.50, p<0.001, treatment effect : F(4,31)=3.10,
p<0.05]. Tukey’s post-hoc test revealed that animals treated with
DMCM and 5 mg/kg of PWZ-029 had longer latency to first entry
to the target quadrant than those treated with solvent (p=0.001,
p<0.001, respectively). Probe trial performance did not differ signifi-
cantly between treatments.
Conclusion : These results suggest that neither non-selective nor b5
subunit-selective negative modulation of GABA A receptors is suf-
ficient to enhance learning and short-term memory in the single-day
MWM spatial task.
PB  - Oxford Univ Press, Oxford
C3  - International Journal of Neuropsychopharmacology
T1  - Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats
VL  - 15
IS  - Supplement 1
SP  - 231
EP  - 231
DO  - 10.1017/S1461145712000508
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1685
ER  - 

@conference{
author = "Timić, Tamara and Divljaković, Jovana and Milinković, Marija M. and Rallapalli, Sundari and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : It is well known that benzodiazepine binding site ligands
influence learning and memory and that the a5 subunit is significantly
involved in cognition enhancement mediated by the negative modu-
lation of GABAA receptor function. PWZ-029, a moderately selective
a5GABA A receptor inverse agonist, improved learning in passive but
not in active avoidance test, without effects on anxiety or muscle tone.
The aim of this study was to investigate effects of PWZ-029 and
DMCM, a non-selective inverse agonist, on learning ability and short-
term memory in Morris water-maze (MWM) test.
Methods : MWM test was conducted 20 minutes after in-
traperitoneal administration of treatments (solvent, 5, 15 or 30 mg/kg
PWZ-029 or 2 mg/kg DMCM) to male Wistar rats. The single-day
MWM task consisted of 3 consecutive blocks of 4 trials lasting maxi-
mally 60 s each and a probe trial. During spatial learning the platform
was hidden in the middle of the NE quadrant.
Results : Two-way ANOVA with one repeated measure (block) and
animals nested in treatment has shown that latency to find the plat-
form, path efficiency and total distance travelled were on the control
level for DMCM and all doses of PWZ-029. Factors block and treat-
ment were significant only for latency to first entry to the NE quadrant
[block effect : F(2,386)=10.50, p<0.001, treatment effect : F(4,31)=3.10,
p<0.05]. Tukey’s post-hoc test revealed that animals treated with
DMCM and 5 mg/kg of PWZ-029 had longer latency to first entry
to the target quadrant than those treated with solvent (p=0.001,
p<0.001, respectively). Probe trial performance did not differ signifi-
cantly between treatments.
Conclusion : These results suggest that neither non-selective nor b5
subunit-selective negative modulation of GABA A receptors is suf-
ficient to enhance learning and short-term memory in the single-day
MWM spatial task.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats",
volume = "15",
number = "Supplement 1",
pages = "231-231",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1685"
}

Timić, T., Divljaković, J., Milinković, M. M., Rallapalli, S., Cook, J. M.,& Savić, M.. (2012). Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 15(Supplement 1), 231-231.
https://doi.org/10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1685

Timić T, Divljaković J, Milinković MM, Rallapalli S, Cook JM, Savić M. Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats. in International Journal of Neuropsychopharmacology. 2012;15(Supplement 1):231-231.
doi:10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1685 .

Timić, Tamara, Divljaković, Jovana, Milinković, Marija M., Rallapalli, Sundari, Cook, James M., Savić, Miroslav, "Non-selective and a(5) subunit-selective negative modulators of GABA(A) receptors in a single-day morris water maze task in rats" in International Journal of Neuropsychopharmacology, 15, no. Supplement 1 (2012):231-231,
https://doi.org/10.1017/S1461145712000508 .,
https://hdl.handle.net/21.15107/rcub_farfar_1685 .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Timić, Tamara
AU  - Radulović, Tamara
AU  - Rallapalli, Sundari
AU  - Milinković, Marija M.
AU  - Divljaković, Jovana
AU  - Batinić, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1673
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze
VL  - 22
IS  - Supplement 2
SP  - S190
EP  - S191
DO  - 10.1016/S0924-977X(12)70274-2
ER  - 

@conference{
author = "Joksimović, Srđan and Timić, Tamara and Radulović, Tamara and Rallapalli, Sundari and Milinković, Marija M. and Divljaković, Jovana and Batinić, Bojan and Cook, James M. and Savić, Miroslav",
year = "2012",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze",
volume = "22",
number = "Supplement 2",
pages = "S190-S191",
doi = "10.1016/S0924-977X(12)70274-2"
}

Joksimović, S., Timić, T., Radulović, T., Rallapalli, S., Milinković, M. M., Divljaković, J., Batinić, B., Cook, J. M.,& Savić, M.. (2012). Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 22(Supplement 2), S190-S191.
https://doi.org/10.1016/S0924-977X(12)70274-2

Joksimović S, Timić T, Radulović T, Rallapalli S, Milinković MM, Divljaković J, Batinić B, Cook JM, Savić M. Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze. in European Neuropsychopharmacology. 2012;22(Supplement 2):S190-S191.
doi:10.1016/S0924-977X(12)70274-2 .

Joksimović, Srđan, Timić, Tamara, Radulović, Tamara, Rallapalli, Sundari, Milinković, Marija M., Divljaković, Jovana, Batinić, Bojan, Cook, James M., Savić, Miroslav, "Effects of PWZ-029, an alpha(5)GABA(A) receptor inverse agonist, on scopolamine-induced spatial learning deficits in the water maze" in European Neuropsychopharmacology, 22, no. Supplement 2 (2012):S190-S191,
https://doi.org/10.1016/S0924-977X(12)70274-2 . .

TY  - JOUR
AU  - Milić, Marija
AU  - Divljaković, Jovana
AU  - Rallapalli, Sundari
AU  - van Linn, Michael
AU  - Timić, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1698
AB  - Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Behavioural Pharmacology
T1  - The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats
VL  - 23
IS  - 2
SP  - 191
EP  - 197
DO  - 10.1097/FBP.0b013e3283512c85
ER  - 

@article{
author = "Milić, Marija and Divljaković, Jovana and Rallapalli, Sundari and van Linn, Michael and Timić, Tamara and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Behavioural Pharmacology",
title = "The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats",
volume = "23",
number = "2",
pages = "191-197",
doi = "10.1097/FBP.0b013e3283512c85"
}

Milić, M., Divljaković, J., Rallapalli, S., van Linn, M., Timić, T., Cook, J. M.,& Savić, M.. (2012). The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats. in Behavioural Pharmacology
Lippincott Williams & Wilkins, Philadelphia., 23(2), 191-197.
https://doi.org/10.1097/FBP.0b013e3283512c85

Milić M, Divljaković J, Rallapalli S, van Linn M, Timić T, Cook JM, Savić M. The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats. in Behavioural Pharmacology. 2012;23(2):191-197.
doi:10.1097/FBP.0b013e3283512c85 .

Milić, Marija, Divljaković, Jovana, Rallapalli, Sundari, van Linn, Michael, Timić, Tamara, Cook, James M., Savić, Miroslav, "The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats" in Behavioural Pharmacology, 23, no. 2 (2012):191-197,
https://doi.org/10.1097/FBP.0b013e3283512c85 . .

TY  - JOUR
AU  - Divljaković, Jovana
AU  - Milić, Marija
AU  - Timić, Tamara
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1668
AB  - Background: Behavioral effects of benzodiazepines following repeated exposure vary according to the intrinsic efficacy of the benzodiazepine studied, treatment schedule and the behavioral parameters evaluated. Methods: We applied the behavioral paradigms of spontaneous locomotor activity, elevated plus maze and grip strength to investigate the sedative, anxiolyfic and myorelaxant effect of acute challenge with 2 mg/kg diazepam administered after 14 days of protracted treatment with 0.5, 2 or 10 mg/kg of diazepam. In addition, we studied the effects of everyday handling and intraperitoneal (ip) administration on animal behavior. Results: Tolerance to the sedative effect of 2 mg/kg diszepam ensued after 14 days of protracted treatment with 2 and 10 mg/kg of diazepam. In contrast, treatment with the lowest dose (0.5 mg/kg) of diazepam resulted in potentiation of the sedative effect of acute challenge with 2 mg/kg diazepam thus confounding the detection of the anxiolytic effect of diazepam. A sensitization-like response to the anxiolytic action of 2 mg/kg diazepam was seen after protracted treatment with the intermediate dose (2 mg/kg); however, anxiolytic effect was absent after protracted administration of the highest dose. Partial tolerance to the muscle relaxant effect of 2 mg/kg diazepam ensued after protracted treatment with diazepam regardless of the dose. Daily handling or ip administration did not alter the behavioral response to acute challenge with 2 mg/kg diazepam in all the three behavioral paradigms studied. Conclusion: The presented results showed that behavioral effects of acute challenge with diazepam were differently affected by the dose administered during protracted treatment.
PB  - Polish Acad Sciences Inst Pharmacology, Krakow
T2  - Pharmacological Reports
T1  - Tolerance liability of diazepam is dependent on the dose used for protracted treatment
VL  - 64
IS  - 5
SP  - 1116
EP  - 1125
DO  - 10.1016/S1734-1140(12)70908-8
ER  - 

@article{
author = "Divljaković, Jovana and Milić, Marija and Timić, Tamara and Savić, Miroslav",
year = "2012",
abstract = "Background: Behavioral effects of benzodiazepines following repeated exposure vary according to the intrinsic efficacy of the benzodiazepine studied, treatment schedule and the behavioral parameters evaluated. Methods: We applied the behavioral paradigms of spontaneous locomotor activity, elevated plus maze and grip strength to investigate the sedative, anxiolyfic and myorelaxant effect of acute challenge with 2 mg/kg diazepam administered after 14 days of protracted treatment with 0.5, 2 or 10 mg/kg of diazepam. In addition, we studied the effects of everyday handling and intraperitoneal (ip) administration on animal behavior. Results: Tolerance to the sedative effect of 2 mg/kg diszepam ensued after 14 days of protracted treatment with 2 and 10 mg/kg of diazepam. In contrast, treatment with the lowest dose (0.5 mg/kg) of diazepam resulted in potentiation of the sedative effect of acute challenge with 2 mg/kg diazepam thus confounding the detection of the anxiolytic effect of diazepam. A sensitization-like response to the anxiolytic action of 2 mg/kg diazepam was seen after protracted treatment with the intermediate dose (2 mg/kg); however, anxiolytic effect was absent after protracted administration of the highest dose. Partial tolerance to the muscle relaxant effect of 2 mg/kg diazepam ensued after protracted treatment with diazepam regardless of the dose. Daily handling or ip administration did not alter the behavioral response to acute challenge with 2 mg/kg diazepam in all the three behavioral paradigms studied. Conclusion: The presented results showed that behavioral effects of acute challenge with diazepam were differently affected by the dose administered during protracted treatment.",
publisher = "Polish Acad Sciences Inst Pharmacology, Krakow",
journal = "Pharmacological Reports",
title = "Tolerance liability of diazepam is dependent on the dose used for protracted treatment",
volume = "64",
number = "5",
pages = "1116-1125",
doi = "10.1016/S1734-1140(12)70908-8"
}

Divljaković, J., Milić, M., Timić, T.,& Savić, M.. (2012). Tolerance liability of diazepam is dependent on the dose used for protracted treatment. in Pharmacological Reports
Polish Acad Sciences Inst Pharmacology, Krakow., 64(5), 1116-1125.
https://doi.org/10.1016/S1734-1140(12)70908-8

Divljaković J, Milić M, Timić T, Savić M. Tolerance liability of diazepam is dependent on the dose used for protracted treatment. in Pharmacological Reports. 2012;64(5):1116-1125.
doi:10.1016/S1734-1140(12)70908-8 .

Divljaković, Jovana, Milić, Marija, Timić, Tamara, Savić, Miroslav, "Tolerance liability of diazepam is dependent on the dose used for protracted treatment" in Pharmacological Reports, 64, no. 5 (2012):1116-1125,
https://doi.org/10.1016/S1734-1140(12)70908-8 . .

TY  - JOUR
AU  - Trisović, Nemanja
AU  - Timić, Tamara
AU  - Divljaković, Jovana
AU  - Rogan, Jelena
AU  - Poleti, Dejan
AU  - Savić, Miroslav
AU  - Uscumlić, Gordana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1649
AB  - Considering the importance of hydantoin derivatives in treatment of status epilepticus, four 5-phenylhydantoins, whose lipophilicities were estimated to be similar to that of phenytoin, were synthesized. Evaluation of their anticonvulsant activities was performed on rats by subcutaneous pentylenetetrazol seizure test and intravenous pentylenetetrazol threshold test, and spontaneous locomotor activity test was used to assess possible sedative effects. X-ray analysis of three compounds suggested that certain analogies might be drawn between interactions in crystal packing and biological interactions responsible for their anticonvulsant activity. It was found that 5-ethyl-5-phenyl-3-propylhydantoin exhibits the most favorable pharmacological properties among the synthesized compounds, i.e., anticonvulsant activity comparable to phenytoin with lower liability for induction of sedation in rats.
PB  - Springer Wien, Wien
T2  - Monatshefte für Chemie Chemical Monthly
T1  - Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents
VL  - 143
IS  - 10
SP  - 1451
EP  - 1457
DO  - 10.1007/s00706-012-0791-8
ER  - 

@article{
author = "Trisović, Nemanja and Timić, Tamara and Divljaković, Jovana and Rogan, Jelena and Poleti, Dejan and Savić, Miroslav and Uscumlić, Gordana",
year = "2012",
abstract = "Considering the importance of hydantoin derivatives in treatment of status epilepticus, four 5-phenylhydantoins, whose lipophilicities were estimated to be similar to that of phenytoin, were synthesized. Evaluation of their anticonvulsant activities was performed on rats by subcutaneous pentylenetetrazol seizure test and intravenous pentylenetetrazol threshold test, and spontaneous locomotor activity test was used to assess possible sedative effects. X-ray analysis of three compounds suggested that certain analogies might be drawn between interactions in crystal packing and biological interactions responsible for their anticonvulsant activity. It was found that 5-ethyl-5-phenyl-3-propylhydantoin exhibits the most favorable pharmacological properties among the synthesized compounds, i.e., anticonvulsant activity comparable to phenytoin with lower liability for induction of sedation in rats.",
publisher = "Springer Wien, Wien",
journal = "Monatshefte für Chemie Chemical Monthly",
title = "Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents",
volume = "143",
number = "10",
pages = "1451-1457",
doi = "10.1007/s00706-012-0791-8"
}

Trisović, N., Timić, T., Divljaković, J., Rogan, J., Poleti, D., Savić, M.,& Uscumlić, G.. (2012). Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents. in Monatshefte für Chemie Chemical Monthly
Springer Wien, Wien., 143(10), 1451-1457.
https://doi.org/10.1007/s00706-012-0791-8

Trisović N, Timić T, Divljaković J, Rogan J, Poleti D, Savić M, Uscumlić G. Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents. in Monatshefte für Chemie Chemical Monthly. 2012;143(10):1451-1457.
doi:10.1007/s00706-012-0791-8 .

Trisović, Nemanja, Timić, Tamara, Divljaković, Jovana, Rogan, Jelena, Poleti, Dejan, Savić, Miroslav, Uscumlić, Gordana, "Synthesis, structural and biological characterization of 5-phenylhydantoin derivatives as potential anticonvulsant agents" in Monatshefte für Chemie Chemical Monthly, 143, no. 10 (2012):1451-1457,
https://doi.org/10.1007/s00706-012-0791-8 . .

TY  - CONF
AU  - Divljaković, Jovana
AU  - Milinković, Marija M.
AU  - Timić, Tamara
AU  - Batinić, Bojan
AU  - Savić, Miroslav
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1509
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Sensitisation and tolerance-like effects of diazepam after repeated administration in rats
VL  - 21
IS  - Supplement 3
SP  - S301
EP  - S301
DO  - 10.1016/S0924-977X(11)70475-8
ER  - 

@conference{
author = "Divljaković, Jovana and Milinković, Marija M. and Timić, Tamara and Batinić, Bojan and Savić, Miroslav",
year = "2011",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Sensitisation and tolerance-like effects of diazepam after repeated administration in rats",
volume = "21",
number = "Supplement 3",
pages = "S301-S301",
doi = "10.1016/S0924-977X(11)70475-8"
}

Divljaković, J., Milinković, M. M., Timić, T., Batinić, B.,& Savić, M.. (2011). Sensitisation and tolerance-like effects of diazepam after repeated administration in rats. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 21(Supplement 3), S301-S301.
https://doi.org/10.1016/S0924-977X(11)70475-8

Divljaković J, Milinković MM, Timić T, Batinić B, Savić M. Sensitisation and tolerance-like effects of diazepam after repeated administration in rats. in European Neuropsychopharmacology. 2011;21(Supplement 3):S301-S301.
doi:10.1016/S0924-977X(11)70475-8 .

Divljaković, Jovana, Milinković, Marija M., Timić, Tamara, Batinić, Bojan, Savić, Miroslav, "Sensitisation and tolerance-like effects of diazepam after repeated administration in rats" in European Neuropsychopharmacology, 21, no. Supplement 3 (2011):S301-S301,
https://doi.org/10.1016/S0924-977X(11)70475-8 . .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Kukić-Marković, Jelena
AU  - Grayer, Renee J.
AU  - Milinković, Marija M.
AU  - Marin, Petar
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Cook, James M.
AU  - Petrović, Silvana
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1336
AB  - We performed a basic behavioral characterization of methanol extracts of four Balkan endemic Stachys taxa: S. anisochila (SA), S. beckeana (SB), S. plumosa (SP) and S. alpina subsp. dinarica (SAD). The behavioral activity of extracts dosed intraperitoneally in the range 100-400 mg/kg was examined in adult male Wistar rats, in the elevated plus maze, spontaneous locomotor activity, and grip strength tests, mainly predictive of anxiolytic, sedative and myorelaxant actions, respectively. All investigated Stachys extracts lacked anxiolytic or myorelaxant activities, while SB at 400 mg/kg exerted an anxiogenic-like effect. The study with the selective antagonist beta-CCt showed that the sedative effect of SAD was only partially mediated by GABAA receptors containing the alpha 1-subunit. While discernible, the behavioral effects of SA and SP were not distinct. In all extracts, chlorogenic acid and verbascoside were identified. In SA, SB, and SAD the flavonoid fraction was constituted of isoscutellarein and hypolaetine glycosides, while in SP chrysoeriol and apigenin glycosides were present. The results reveal the psychotropic potential of four endemic Stachys taxa, of which SAD appeared most promising as a natural sedative. Copyright
PB  - Wiley-Blackwell, Malden
T2  - Phytotherapy Research
T1  - Behavioural Characterization of Four Endemic Stachys Taxa
VL  - 24
IS  - 9
SP  - 1309
EP  - 1316
DO  - 10.1002/ptr.3106
ER  - 

@article{
author = "Savić, Miroslav and Kukić-Marković, Jelena and Grayer, Renee J. and Milinković, Marija M. and Marin, Petar and Divljaković, Jovana and van Linn, Michael and Cook, James M. and Petrović, Silvana",
year = "2010",
abstract = "We performed a basic behavioral characterization of methanol extracts of four Balkan endemic Stachys taxa: S. anisochila (SA), S. beckeana (SB), S. plumosa (SP) and S. alpina subsp. dinarica (SAD). The behavioral activity of extracts dosed intraperitoneally in the range 100-400 mg/kg was examined in adult male Wistar rats, in the elevated plus maze, spontaneous locomotor activity, and grip strength tests, mainly predictive of anxiolytic, sedative and myorelaxant actions, respectively. All investigated Stachys extracts lacked anxiolytic or myorelaxant activities, while SB at 400 mg/kg exerted an anxiogenic-like effect. The study with the selective antagonist beta-CCt showed that the sedative effect of SAD was only partially mediated by GABAA receptors containing the alpha 1-subunit. While discernible, the behavioral effects of SA and SP were not distinct. In all extracts, chlorogenic acid and verbascoside were identified. In SA, SB, and SAD the flavonoid fraction was constituted of isoscutellarein and hypolaetine glycosides, while in SP chrysoeriol and apigenin glycosides were present. The results reveal the psychotropic potential of four endemic Stachys taxa, of which SAD appeared most promising as a natural sedative. Copyright",
publisher = "Wiley-Blackwell, Malden",
journal = "Phytotherapy Research",
title = "Behavioural Characterization of Four Endemic Stachys Taxa",
volume = "24",
number = "9",
pages = "1309-1316",
doi = "10.1002/ptr.3106"
}

Savić, M., Kukić-Marković, J., Grayer, R. J., Milinković, M. M., Marin, P., Divljaković, J., van Linn, M., Cook, J. M.,& Petrović, S.. (2010). Behavioural Characterization of Four Endemic Stachys Taxa. in Phytotherapy Research
Wiley-Blackwell, Malden., 24(9), 1309-1316.
https://doi.org/10.1002/ptr.3106

Savić M, Kukić-Marković J, Grayer RJ, Milinković MM, Marin P, Divljaković J, van Linn M, Cook JM, Petrović S. Behavioural Characterization of Four Endemic Stachys Taxa. in Phytotherapy Research. 2010;24(9):1309-1316.
doi:10.1002/ptr.3106 .

Savić, Miroslav, Kukić-Marković, Jelena, Grayer, Renee J., Milinković, Marija M., Marin, Petar, Divljaković, Jovana, van Linn, Michael, Cook, James M., Petrović, Silvana, "Behavioural Characterization of Four Endemic Stachys Taxa" in Phytotherapy Research, 24, no. 9 (2010):1309-1316,
https://doi.org/10.1002/ptr.3106 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Huang, Shengming
AU  - Ramerstorfer, Joachim
AU  - Milinković, Marija M.
AU  - Divljaković, Jovana
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Savić, Miroslav
AU  - Cook, James M.
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1350
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile
VL  - 20
IS  - Supplement 3
SP  - S260
EP  - S260
DO  - 10.1016/S0924-977X(10)70331-X
ER  - 

@conference{
author = "Joksimović, Srđan and Huang, Shengming and Ramerstorfer, Joachim and Milinković, Marija M. and Divljaković, Jovana and Roth, Brian L. and Sieghart, Werner and Savić, Miroslav and Cook, James M.",
year = "2010",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile",
volume = "20",
number = "Supplement 3",
pages = "S260-S260",
doi = "10.1016/S0924-977X(10)70331-X"
}

Joksimović, S., Huang, S., Ramerstorfer, J., Milinković, M. M., Divljaković, J., Roth, B. L., Sieghart, W., Savić, M.,& Cook, J. M.. (2010). SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 20(Supplement 3), S260-S260.
https://doi.org/10.1016/S0924-977X(10)70331-X

Joksimović S, Huang S, Ramerstorfer J, Milinković MM, Divljaković J, Roth BL, Sieghart W, Savić M, Cook JM. SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile. in European Neuropsychopharmacology. 2010;20(Supplement 3):S260-S260.
doi:10.1016/S0924-977X(10)70331-X .

Joksimović, Srđan, Huang, Shengming, Ramerstorfer, Joachim, Milinković, Marija M., Divljaković, Jovana, Roth, Brian L., Sieghart, Werner, Savić, Miroslav, Cook, James M., "SH-I-048A, a novel positive modulator of GABA-A receptor: in vitro and behavioral profile" in European Neuropsychopharmacology, 20, no. Supplement 3 (2010):S260-S260,
https://doi.org/10.1016/S0924-977X(10)70331-X . .

TY  - CONF
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Milinković, Marija M.
AU  - Yin, Wenyuan
AU  - Batinić, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1352
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment
VL  - 20
IS  - Supplement 3
SP  - S261
EP  - S262
DO  - 10.1016/S0924-977X(10)70334-5
ER  - 

@conference{
author = "Divljaković, Jovana and van Linn, Michael and Milinković, Marija M. and Yin, Wenyuan and Batinić, Bojan and Cook, James M. and Savić, Miroslav",
year = "2010",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment",
volume = "20",
number = "Supplement 3",
pages = "S261-S262",
doi = "10.1016/S0924-977X(10)70334-5"
}

Divljaković, J., van Linn, M., Milinković, M. M., Yin, W., Batinić, B., Cook, J. M.,& Savić, M.. (2010). Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 20(Supplement 3), S261-S262.
https://doi.org/10.1016/S0924-977X(10)70334-5

Divljaković J, van Linn M, Milinković MM, Yin W, Batinić B, Cook JM, Savić M. Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment. in European Neuropsychopharmacology. 2010;20(Supplement 3):S261-S262.
doi:10.1016/S0924-977X(10)70334-5 .

Divljaković, Jovana, van Linn, Michael, Milinković, Marija M., Yin, Wenyuan, Batinić, Bojan, Cook, James M., Savić, Miroslav, "Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment" in European Neuropsychopharmacology, 20, no. Supplement 3 (2010):S261-S262,
https://doi.org/10.1016/S0924-977X(10)70334-5 . .

TY  - CONF
AU  - Milinković, Marija M.
AU  - Samardžić, Janko
AU  - Divljaković, Jovana
AU  - Joksimović, Srđan
AU  - Timić, Tamara
AU  - Savić, Miroslav
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1347
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Midazolam impairs acquisition but not consolidation in water maze paradigm
VL  - 20
IS  - Supplement 3
SP  - S259
EP  - S260
DO  - 10.1016/S0924-977X(10)70330-8
ER  - 

@conference{
author = "Milinković, Marija M. and Samardžić, Janko and Divljaković, Jovana and Joksimović, Srđan and Timić, Tamara and Savić, Miroslav",
year = "2010",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Midazolam impairs acquisition but not consolidation in water maze paradigm",
volume = "20",
number = "Supplement 3",
pages = "S259-S260",
doi = "10.1016/S0924-977X(10)70330-8"
}

Milinković, M. M., Samardžić, J., Divljaković, J., Joksimović, S., Timić, T.,& Savić, M.. (2010). Midazolam impairs acquisition but not consolidation in water maze paradigm. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 20(Supplement 3), S259-S260.
https://doi.org/10.1016/S0924-977X(10)70330-8

Milinković MM, Samardžić J, Divljaković J, Joksimović S, Timić T, Savić M. Midazolam impairs acquisition but not consolidation in water maze paradigm. in European Neuropsychopharmacology. 2010;20(Supplement 3):S259-S260.
doi:10.1016/S0924-977X(10)70330-8 .

Milinković, Marija M., Samardžić, Janko, Divljaković, Jovana, Joksimović, Srđan, Timić, Tamara, Savić, Miroslav, "Midazolam impairs acquisition but not consolidation in water maze paradigm" in European Neuropsychopharmacology, 20, no. Supplement 3 (2010):S259-S260,
https://doi.org/10.1016/S0924-977X(10)70330-8 . .

TY  - CONF
AU  - Milinković, Marija M.
AU  - Savić, Miroslav
AU  - Huang, Shengming
AU  - Furtmueller, Roman
AU  - Majumder, Samarpan
AU  - Samardžić, Janko
AU  - Divljaković, Jovana
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1173
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Jy-xhe-053, a benzodiazepine ligand less efficacious at GABAA receptors containing alpha1 and alpha5 than alpha2 and alpha3 subunits
VL  - 19
IS  - Supplement 3
SP  - S296
EP  - S296
DO  - 10.1016/S0924-977X(09)70438-9
ER  - 

@conference{
author = "Milinković, Marija M. and Savić, Miroslav and Huang, Shengming and Furtmueller, Roman and Majumder, Samarpan and Samardžić, Janko and Divljaković, Jovana and Roth, Brian L. and Sieghart, Werner and Cook, James M.",
year = "2009",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Jy-xhe-053, a benzodiazepine ligand less efficacious at GABAA receptors containing alpha1 and alpha5 than alpha2 and alpha3 subunits",
volume = "19",
number = "Supplement 3",
pages = "S296-S296",
doi = "10.1016/S0924-977X(09)70438-9"
}

Milinković, M. M., Savić, M., Huang, S., Furtmueller, R., Majumder, S., Samardžić, J., Divljaković, J., Roth, B. L., Sieghart, W.,& Cook, J. M.. (2009). Jy-xhe-053, a benzodiazepine ligand less efficacious at GABAA receptors containing alpha1 and alpha5 than alpha2 and alpha3 subunits. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 19(Supplement 3), S296-S296.
https://doi.org/10.1016/S0924-977X(09)70438-9

Milinković MM, Savić M, Huang S, Furtmueller R, Majumder S, Samardžić J, Divljaković J, Roth BL, Sieghart W, Cook JM. Jy-xhe-053, a benzodiazepine ligand less efficacious at GABAA receptors containing alpha1 and alpha5 than alpha2 and alpha3 subunits. in European Neuropsychopharmacology. 2009;19(Supplement 3):S296-S296.
doi:10.1016/S0924-977X(09)70438-9 .

Milinković, Marija M., Savić, Miroslav, Huang, Shengming, Furtmueller, Roman, Majumder, Samarpan, Samardžić, Janko, Divljaković, Jovana, Roth, Brian L., Sieghart, Werner, Cook, James M., "Jy-xhe-053, a benzodiazepine ligand less efficacious at GABAA receptors containing alpha1 and alpha5 than alpha2 and alpha3 subunits" in European Neuropsychopharmacology, 19, no. Supplement 3 (2009):S296-S296,
https://doi.org/10.1016/S0924-977X(09)70438-9 . .