Role of CRF in ethanol negative reinforcement

Scripps Research Institute, La Jolla CA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The neurobiological basis for the negative reinforcement important for the development of alcoholism and the vulnerability to relapse is believed to include counteradaptive neurochemical events within the brain emotional systems, such as the stress systems. Corticotropin releasing factor has been implicated in the motivational changes associated with ethanol withdrawal and the increased ethanol self-administration associated with withdrawal in the rat. CRF activity is recruited in alcohol dependent animals during withdrawal and protracted abstinence. Dependent animals also display enhanced stress-like responses and enhanced ethanol self-administration during acute withdrawal and protracted abstinence, effects reversed by CRF antagonists. The experiments in this proposal are designed to study the role of CRF1 and CRF2 receptors in specific brain regions in mediating the enhanced drinking associated with ethanol withdrawal. Further, the role of CRF2 receptors and CRF1 and CRF2 receptor expression in mediating the enhanced CRF release during ethanol withdrawal will be examined. The overall hypothesis is that increased CRF activity in the extended amygdala is responsible for the enhanced drinking associated with withdrawal. [unreadable] [unreadable]