Role of the GABA_a and GABA_b receptors of the central nucleus of the amygdala in compulsive cocaine-seeking behavior in male rats.

RATIONALE:Compulsive cocaine use, defined as the continued use despite the dire consequences, is a hallmark of cocaine addiction. Thus, understanding the brain mechanism regulating the compulsive cocaine-seeking and cocaine-taking behaviors is essential to understand cocaine addiction and the key to identification of the molecular targets for the development of medications against this condition. OBJECTIVE:This study aimed to determine how the GABA_a and GABA_b receptors of the central nucleus of the amygdala (CeA) regulate the compulsive cocaine-seeking behavior. METHODS:Male Wistar outbred rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) under a chained schedule. The compulsive cocaine-seeking behavior was measured as the cocaine-seeking behavior in the face of footshock punishment. The role of the GABA receptors of CeA in the regulation of such behavior was determined by measuring the dose-dependent effects of the GABA_a agonist muscimol or the GABA_b agonist baclofen bilaterally microinjected into the CeA on the punished cocaine-seeking behavior. RESULTS:The cocaine-seeking behavior was inhibited by footshock punishment in an intensity-dependent manner. Both muscimol and baclofen dose-dependently increased the punished cocaine-seeking behavior. However, the potency of muscimol but not baclofen was negatively correlated with the effects of punishment. CONCLUSION:These data indicate that the CeA GABA_a receptors play a key role in the regulation of the compulsive cocaine-seeking behavior and suggest that an increase in the function of the GABA_a receptors possibly induced by cocaine or genetic factors may be an important mechanism involved in the development of or vulnerability to the compulsive cocaine use and addiction.

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