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

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.