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Trends Neurosci. 2007 Aug;30(8):399-406. Epub 2007 Jul 16.

A key role for corticotropin-releasing factor in alcohol dependence.

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  • 1Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), NIH, 10 Center Dr., 1/5334, Bethesda, MD 20892, USA. markus.heilig@mail.nih.gov


Recent data indicate that alcohol dependence induces long-term neuroadaptations that recruit a negative emotional state. This leads to excessive alcohol ingestion motivated by relief of negative emotionality. A key mechanism in this transition to negative reinforcement is a recruitment of corticotropin-releasing factor (CRF) signaling within the amygdala. Long term upregulation of CRF(1) receptors is observed in the amygdala following a history of dependence, and CRF antagonists selectively block emotionality, excessive alcohol drinking and stress-induced reinstatement of alcohol-seeking in post-dependent animals. Innate upregulation of CRF(1) receptor expression mimics the post-dependent phenotype, both with regard to emotional responses and ethanol self-administration. Therefore, the CRF system is emerging as a key element of the neuroadaptive changes driving alcoholism and as a major target for its treatment.

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