A CRF2 agonist administered into the central nucleus of the amygdala decreases ethanol self-administration in ethanol-dependent rats

Abstract

Alcohol dependence is characterized by excessive consumption, loss of control over intake and the presence of a withdrawal syndrome, including both motivational and physical symptoms. Previous studies have implicated the brain corticotropin-releasing factor (CRF) stress systems in mediating the negative emotional state associated with ethanol withdrawal. CRF1 receptor-specific antagonists, administered systemically, and CRF receptor subtype nonspecific antagonists, administered into the central nucleus of the amygdala (CeA), selectively decrease the anxiety-like behaviors and increased ethanol self-administration associated with ethanol withdrawal. In the present study, we investigated the role of CRF2 receptors within the CeA in mediating ethanol self-administration in ethanol-dependent and nondependent animals. Male Wistar rats were made dependent on ethanol using an intermittent ethanol vapor exposure paradigm. Nondependent animals received similar conditions but were exposed to air only. Following 2 h of withdrawal from ethanol vapors, ethanol and water self-administration were measured following administration of urocortin 3, a highly selective CRF2 agonist, in the CeA. In dependent rats, urocortin 3 (0.1 μg/μl and 0.5 μg/μl) decreased ethanol self-administration, with no effect on water self-administration. In nondependent rats, urocortin 3 (0.5 μg/μl) increased ethanol self-administration, with no effect on water self-administration. These data demonstrate an opposing role of the CRF2 receptor subtype within the CeA in mediating ethanol self-administration in withdrawn, dependent and nondependent rats.