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  - 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  - Joksimović, Srđan
AU  - Savić, Miroslav
AU  - Milinković, Marija M.
AU  - van Linn, Michael
AU  - Ramerstorfer, Joachim
AU  - Majumder, Samarpan
AU  - Yin, Wenyuan
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1172
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?
VL  - 19
IS  - Supplement 3
SP  - S297
EP  - S297
DO  - 10.1016/S0924-977X(09)70440-7
ER  - 

@conference{
author = "Joksimović, Srđan and Savić, Miroslav and Milinković, Marija M. and van Linn, Michael and Ramerstorfer, Joachim and Majumder, Samarpan and Yin, Wenyuan and Roth, Brian L. and Sieghart, Werner and Cook, James M.",
year = "2009",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?",
volume = "19",
number = "Supplement 3",
pages = "S297-S297",
doi = "10.1016/S0924-977X(09)70440-7"
}

Joksimović, S., Savić, M., Milinković, M. M., van Linn, M., Ramerstorfer, J., Majumder, S., Yin, W., Roth, B. L., Sieghart, W.,& Cook, J. M.. (2009). WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 19(Supplement 3), S297-S297.
https://doi.org/10.1016/S0924-977X(09)70440-7

Joksimović S, Savić M, Milinković MM, van Linn M, Ramerstorfer J, Majumder S, Yin W, Roth BL, Sieghart W, Cook JM. WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?. in European Neuropsychopharmacology. 2009;19(Supplement 3):S297-S297.
doi:10.1016/S0924-977X(09)70440-7 .

Joksimović, Srđan, Savić, Miroslav, Milinković, Marija M., van Linn, Michael, Ramerstorfer, Joachim, Majumder, Samarpan, Yin, Wenyuan, Roth, Brian L., Sieghart, Werner, Cook, James M., "WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?" in European Neuropsychopharmacology, 19, no. Supplement 3 (2009):S297-S297,
https://doi.org/10.1016/S0924-977X(09)70440-7 . .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Obradović, Dragan I.
AU  - Ugrešić, Nenad
AU  - Cook, James M.
AU  - Yin, Wenyuan
AU  - van Linn, Michael
AU  - Bokonjić, Dubravko
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/828
AB  - Benzodiazepine site inverse agonists may increase or decrease locomotor activity in rodents, depending on the experimental settings. We have compared the behavioral responses to environmental novelty of rats treated with the non-selective inverse agonist DMCM (2 mg/kg) and the alpha(1)-subunit affinity-selective inverse agonist 3-EBC (15 mg/kg). The behavior in spontaneous locomotor assay (during 45 min) and elevated plus maze (EPM) was automatically recorded. In the EPM, general activity-related parameters were similarly decreased, whereas only DMCM inhibited open-arm activity. In the locomotor assay, both compounds depressed locomotion in the first 15 min and activity in the central zone of the chamber. However, the influence of 3-EBC was less pronounced. The alpha(1)-subunit selective antagonist beta-CCt (15 mg/kg) attenuated locomotor depression, but not the central-zone avoidance elicited by DMCM. When habituated to the chamber, DMCM-treated animals emitted a plateau phase of activity, which disappeared by adding beta-CCt. Hence, inhibition of activity in exposed areas may be mediated by non-alpha(1)-subunits, whereas both alpha(1) and non-alpha(1)-subunits may participate in suppression of activity in more protective areas of an apparatus. Hyperlocomotion in habituated animals may depend primarily on the alpha(1)-subunit. Moreover, the bimodal influence of inverse agonists on locomotion can be biphasic, observable in the same experiment.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Pharmacology Biochemistry and Behavior
T1  - Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence
VL  - 84
IS  - 1
SP  - 35
EP  - 42
DO  - 10.1016/j.pbb.2006.04.001
ER  - 

@article{
author = "Savić, Miroslav and Obradović, Dragan I. and Ugrešić, Nenad and Cook, James M. and Yin, Wenyuan and van Linn, Michael and Bokonjić, Dubravko",
year = "2006",
abstract = "Benzodiazepine site inverse agonists may increase or decrease locomotor activity in rodents, depending on the experimental settings. We have compared the behavioral responses to environmental novelty of rats treated with the non-selective inverse agonist DMCM (2 mg/kg) and the alpha(1)-subunit affinity-selective inverse agonist 3-EBC (15 mg/kg). The behavior in spontaneous locomotor assay (during 45 min) and elevated plus maze (EPM) was automatically recorded. In the EPM, general activity-related parameters were similarly decreased, whereas only DMCM inhibited open-arm activity. In the locomotor assay, both compounds depressed locomotion in the first 15 min and activity in the central zone of the chamber. However, the influence of 3-EBC was less pronounced. The alpha(1)-subunit selective antagonist beta-CCt (15 mg/kg) attenuated locomotor depression, but not the central-zone avoidance elicited by DMCM. When habituated to the chamber, DMCM-treated animals emitted a plateau phase of activity, which disappeared by adding beta-CCt. Hence, inhibition of activity in exposed areas may be mediated by non-alpha(1)-subunits, whereas both alpha(1) and non-alpha(1)-subunits may participate in suppression of activity in more protective areas of an apparatus. Hyperlocomotion in habituated animals may depend primarily on the alpha(1)-subunit. Moreover, the bimodal influence of inverse agonists on locomotion can be biphasic, observable in the same experiment.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Pharmacology Biochemistry and Behavior",
title = "Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence",
volume = "84",
number = "1",
pages = "35-42",
doi = "10.1016/j.pbb.2006.04.001"
}

Savić, M., Obradović, D. I., Ugrešić, N., Cook, J. M., Yin, W., van Linn, M.,& Bokonjić, D.. (2006). Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence. in Pharmacology Biochemistry and Behavior
Pergamon-Elsevier Science Ltd, Oxford., 84(1), 35-42.
https://doi.org/10.1016/j.pbb.2006.04.001

Savić M, Obradović DI, Ugrešić N, Cook JM, Yin W, van Linn M, Bokonjić D. Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence. in Pharmacology Biochemistry and Behavior. 2006;84(1):35-42.
doi:10.1016/j.pbb.2006.04.001 .

Savić, Miroslav, Obradović, Dragan I., Ugrešić, Nenad, Cook, James M., Yin, Wenyuan, van Linn, Michael, Bokonjić, Dubravko, "Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence" in Pharmacology Biochemistry and Behavior, 84, no. 1 (2006):35-42,
https://doi.org/10.1016/j.pbb.2006.04.001 . .