Role of the GABA and GABA 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 and GABA 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 agonist muscimol or the GABA 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 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 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.