The present study was conducted to investigate whether several GABAergic drugs could affect immobility in the behavioral “despair” test (swimming test). The subacute (3 injections) treatment with the GABA-B agonist baclofen 0.5 mg/kg (BC05) partially antagonised the antiimmobility action of imipramine (IMI), whereas muscimol 0.00125 mg/kg (MU ; GABA-A agonist) did not affect the imipramine effect on immobility. The highest doses of baclofen alone increased immobility time, and no effect of muscimol alone was observed on this measure. Other experiments indicated that different doses of δ-α-aminovaleric acid (a GABA-B antagonist and GABA-A agonist) or progabide (a GABA A/B agonist with clinical antidepressive properties) did not modify immobility time. On the other hand, sodium valproate (VPA), chronically administered, was effective in reducing the time of immobility of rats in the swimming test, at doses which did not alter motor activity in an open field test. Since there is evidence indicating that valproate can be considered as a GABA-mimetic agent, the present data is consistent with other results showing an antidepressant-like activity of agents which enhance GABAergic transmission.