PHARMACOETHOLOGICAL INVESTIGATION OF GABA ERGIC MECHANISMS OF DEPRESSION-LIKE BEHAVIOR IN MICE

It is known that repeated stress may result in depression-like alterat ions of behavior. This behavior is characterized by decreased social e xploratory activity and increase in occurrence of defensive postures i n a social interaction test in mice. The passive defensive,behavior is effectively antagonized by antidepressant drugs thus providing a usef ul animal model of depression, Effects of several GABAergic drugs were studied in opponent test in individually housed male mice. For two we eks preceding the test, mice were repeatedly exposed to foot shock sti mulation and/or social confrontation with an aggressive mouse. Muscimo l, a selective agonist of GABA(A) receptors, decreased the frequency a nd duration of defensive postures and increased the duration of some f orms of individual activity (grooming and eating), like the agonist of GABA(B) receptors baclofen, Muscimol was the only compound that facil itated exploratory activity towards an unfamiliar partner and did not suppress the locomotion. Effects of another agonist of GABA(B) recepto rs phenibut and inhibitor of GABA transaminase valproate Na were less specific and consisted in general suppression of behavior (prevalence of static forms of behavior). It can be thought that GABA(A) receptors are essential for regulation of depression-like behavior of mice.