INTERACTIONS BETWEEN DOPAMINE AND GABA IN THE CONTROL OF AMBULATORY ACTIVITY AND NEOPHOBIA IN THE MOUSE

Ambulatory activity in a familiar and novel environment as well as the time spent in a novel environment were evaluated using the free explo ratory paradigm. Male mice treated with D-amphetamine, 2 mg/kg, displa yed enhanced ambulatory activity in the familiar environment. The time spent in the novel environment was reduced by amphetamine, 1 and 2 mg /kg. The GABA transaminase inhibitor gamma-acetylen GABA (GAG) reduced ambulatory activity and rearing as well as the time spent in the nove l environment. The mixed GABA(A)/GABA(B) agonist progabide, 200 mg/kg, reduced rearing both in the familiar and novel environments without a ffecting the time spent in the novel environment. Amphetamine, 1 mg/kg , was then combined with ineffective doses of GAG and progabide (50 an d 100 mg/kg, respectively). The GABAergics did not reliably modify the effects of amphetamine on the time spent in the novel environment. Am bulatory activity and rearing were reduced both in comparison to amphe tamine + saline and to control. These data show that GABAergic drugs a re potentiated by enhanced dopaminergic neurotransmission with regard to their actions on ambulatory activity and rearing. The effects of pr ogabide + amphetamine were then evaluated after treatment with the GAB A(A) antagonist bicuculline or the GABA(B) antagonist CGP 35348. Neith er bicuculline, 1 mg/kg, nor CGP 35348, 100 mg/kg, blocked the actions of progabide. The combined treatment with both antagonists was also u nable to reduce the effects of progabide. These data suggest that the interaction between amphetamine and progabide with regard to motor eff ects depends on a non-GABA(A), non-GABA(B) receptor. (C) 1998 Elsevier Science Inc.