A key role for corticotropin-releasing factor in alcohol dependenceTrends 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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