Behavioral aspects of GABA-dopamine interrelationships in the monkey

The interrelationships between dopamine and GABA have been most actively pursued in animal models of schizophrenia and the movement disorders of tardive dyskinesia and Huntington's disease. At present, the conflicting evidence about inhibitory/excitatory influences of GABA on dopaminergic function raises interesting practical and theoretical questions for research and future treatment strategies. To investigate further the interactions between dopamine and GABA, monkeys that demonstrated behavioral hypersensitivity to dopamine agonists after long-term haloperidol treatment were tested with apomorphine 0.25 mg/kg, muscimol 0.25 mg/kg, 0.50 mg/kg, and 1.0 mg/kg, and γ-acetylenic GABA (GAG) 50 mg/kg and 100 mg/kg. During each trial, conducted at least 3 days apart, behavioral changes of locomotion, stereotypy, oral hyperkinesia, eye blinking rate, and arousal were scored. Muscimol and GAG decreased but did not suppress the apomorphine-induced hyperkinetic syndrome. These results are consistent with the hypothesis that GABA has an inhibitory influence on dopaminergic mechanisms, through the limited effects suggest a secondary or modulatory function for GABA rather than a primary role in dopamine-mediated behavior.