THE INHIBITORY EFFECTS ON SEXUAL-BEHAVIOR AND AMBULATORY ACTIVITY OF THE MIXED GABA(A) GABA(B) AGONIST PROGABIDE ARE DIFFERENTIALLY BLOCKEDBY GABA RECEPTOR ANTAGONISTS/

Progabide inhibited male rat sexual behavior at a dose of 200 mg/kg. T his dose had only modest effects on ambulatory activity and no effect at all on motor coordination as evaluated by a rotarod test. The GABA( A) antagonist bicuculline, at a dose of 1 mg/kg, blocked the effects o f progabide on sex behavior. In contrast, the GABA(B) antagonist CGP 3 5348, at doses of 50 and 100 mg/kg, was ineffective. These doses have previously been shown to block the actions of baclofen on sexual behav ior. It was concluded that the GABA(A) but not the GABA(B) receptor is important for the inhibitory effects of progabide on that behavior. T he actions of progabide on ambulatory activity were not blocked by bic uculline or CGP 35348 at any of the doses used (up to 2 and 200 mg/kg, respectively). Even the combination of both antagonists was ineffecti ve. This suggests that the motor effects of progabide are mediated by either a non-GABAergic receptor or by a subtype of the GABA(A) or the GABA(B) receptor that is not sensitive to the antagonists. Present res ults show that the effects of progabide on motor functions depend on m echanisms different from those involved in its effects on sexual behav ior. They further suggest that the GABA(A) receptor may be important f or drug actions on male sexual behavior.