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The influence of an a5GABAA selective agonist XLi356 on rats' performance in morris water maze

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Authors
Milinković, Marija M.
Timić, Tamara
Divljaković, Jovana
Joksimović, Srđan
Rallapalli, Sundari
Cook, James M.
Savić, Miroslav
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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-New...man-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.

Source:
International Journal of Neuropsychopharmacology, 2012, 15, Supplement 1, 231-231
Publisher:
  • Oxford Univ Press, Oxford
Note:
  • 28th CINP World Congress of Neuropsychopharmacology, Stockholm, Sweden, 3–7 June 2012

DOI: 10.1017/S1461145712000508

ISSN: 1461-1457

WoS: 000209062500840

[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_farfar_1660
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1660
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
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 .

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