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Alcohol Clin Exp Res. 2011 Oct;35(10):1876-83. doi: 10.1111/j.1530-0277.2011.01532.x. Epub 2011 May 16.

Involvement of arginine vasopressin and V1b receptor in alcohol drinking in Sardinian alcohol-preferring rats.

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Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10065, USA.



Recent animal studies have shown that the level of stress-responsive arginine vasopressin (AVP) gene expression in the amygdala is increased during early withdrawal from long-term heroin or cocaine administration. The selective AVP V1b receptor antagonist SSR149415 (capable of exerting antidepressant-like and anxiolytic effects in animal models) also blocked stress-induced reinstatement of drug-seeking behavior. This study was undertaken to investigate the effects of alcohol and to determine whether (i) there are genetically determined differences in basal AVP mRNA levels in the medial/central amygdala (Me/CeA) and medial hypothalamus (MH) between selectively bred Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats; (ii) the AVP mRNA levels are altered by long-term alcohol drinking in sP rats; and (iii) the V1b receptor antagonist SSR149415 alters alcohol drinking in sP rats.


In Experiment 1, AVP mRNA levels were measured in the Me/CeA and MH of alcohol-naïve sP and sNP rats, and sP rats exposed to the standard, homecage 2-bottle "alcohol versus water" choice regimen 24 h/d for 17 days. In Experiment 2, SSR149415 (0, 3, 10, or 30 mg/kg; intraperitoneal) was acutely administered 30 minutes before lights off to alcohol-experienced sP rats. Alcohol, water, and food intake were monitored 6 and 24 hours later.


We found higher basal AVP mRNA levels in both Me/CeA and MH of alcohol-naïve sP than sNP rats; alcohol consumption decreased AVP mRNA levels in both brain regions of sP rats, suggesting genetically determined differences between the 2 rat lines and in the effects of alcohol drinking in sP rats. Acute treatment with SSR149415 significantly reduced alcohol intake of sP rats.


The stress-responsive AVP/V1b receptor system is 1 component of the neural circuitry underlying high alcohol drinking in sP rats.


Sardinian alcohol-preferring (sP) and -nonpreferring (sNP) rats; V1b receptor; alcohol drinking; amygdala; arginine vasopressin; gene expression

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