Chapter 16 - The Corticotropin Releasing Factor System and Alcohol Consumption

Abstract

Excessive alcohol consumption leading to dependence is accompanied by adaptive changes in neurocircuits regulating reward, mood, and stress response. The corticotropin releasing factor (CRF) system is at the helm of these neurocircuits, and is a major contributor to regulation of alcohol use and dependence. Early studies focused on the CRF as a potential mediator of dependence. Recent studies recognize that CRF is not the only player in this process. Ligands of CRF receptors include endogenous peptides urocortins (Ucn1, Ucn2, and Ucn3). Midbrain Ucn1-expressing neurons are selectively activated during alcohol drinking. CRF, acting on CRF1 receptors, regulates alcohol intake, but can do so not in an ethanol-specific way. Ucn1 capable of acting on both CRF1 and CRF2, and Ucn3 acting on CRF2 receptors can regulate alcohol intake and preference, in a drug-specific manner. Future development of therapeutics to combat alcohol dependence would benefit from understanding intricacies of the CRF system.