A key role for corticotropin-releasing factor in alcohol dependence
Trends in Neurosciences Article in Press, Corrected Proof 16 July 2007



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 CRF₁ 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 CRF₁ 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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Reprint Request E-Mail: markus.heilig@mail.nih.gov
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