Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse

Pharmacology, Biochemistry, and Behavior
A Agmo, C Belzung

Abstract

Ambulatory activity in a familiar and novel environment as well as the time spent in a novel environment were evaluated using the free exploratory paradigm. Male mice treated with D-amphetamine, 2 mg/kg, displayed 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 novel environment. The mixed GABA(A)/GABA(B) agonist progabide, 200 mg/kg, reduced rearing both in the familiar and novel environments without affecting the time spent in the novel environment. Amphetamine, 1 mg/kg, was then combined with ineffective doses of GAG and progabide (50 and 100 mg/kg, respectively). The GABAergics did not reliably modify the effects of amphetamine on the time spent in the novel environment. Ambulatory activity and rearing were reduced both in comparison to amphetamine + saline and to control. These data show that GABAergic drugs are potentiated by enhanced dopaminergic neurotransmission with regard to their actions on ambulatory activity and rearing. The effects of progabide + amphetamine were then evaluated after treatment...Continue Reading

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