Evidence that vasopressin V

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Abstract:

ABSTRACT

Alcoholism is a devastating condition that represents a progression from initial alcohol use to dependence. Although most individuals are capable of consuming alcohol in a limited fashion, the development of alcohol dependence in a subset of individuals is often associated with negative emotional states (including anxiety and depression). Since the alleviation of this negative motivational state via excessive alcohol consumption often becomes a central goal of alcoholics, the transition from initial use to dependence is postulated to be associated with a transition from positive to negative reinforcement mechanisms. Vasopressin is a neuropeptide known to potentiate the effects of CRF on the HPA axis, and emerging evidence also suggests a role for centrally located vasopressin acting on V1b receptors in the regulation of stress‐ and anxiety‐like behaviors in rodents. The present study determined state‐dependent alterations in vasopressin/V1bR signaling in an animal model of ethanol dependence. The V1bR antagonist SSR149415 dose‐dependently reduced excessive levels of ethanol self‐administration observed in dependent animals without affecting the limited levels of ethanol drinking in non‐dependent animals. Ethanol self‐administration reduced V1b receptor levels in the basolateral amygdala of non‐dependent animals, a neuroadaptation that could theoretically facilitate the positive reinforcing effects of alcohol. In contrast, V1bR levels were seemingly restored in ethanol‐dependent rats, a switch that may in part underlie a transition from positive to negative reinforcement mechanisms with dependence. Together, our data suggest a key role for vasopressin/V1bR signaling in the transition to ethanol dependence.

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1369-1600.2010.00291.x

Affiliations: 1: Committee on the Neurobiology of Addictive Disorders, USA 2: Department of Chemistry, The Scripps Research Institute, USA

Publication date: January 1, 2012

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