Effects of CRF₁-Receptor and Opioid-Receptor Antagonists on Dependence-Induced Increases in Alcohol Drinking by Alcohol-Preferring (P) Rats
Alcoholism: Clinical and Experimental Research Published Online: 10 Jul 2008

Selective breeding of rats over generations and induction of alcohol dependence via chronic vapor inhalation both enhance alcohol consumption in animal models.

The purpose of this study was to determine whether dependence-induced increases in alcohol consumption by P rats is sensitive to naltrexone, a general opioid receptor antagonist (but with highest affinity at the μ-opioid receptor at low doses), and the recently characterized small molecule CRF₁-receptor antagonist MPZP (N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine).

MPZP attenuated dependence-induced increases in alcohol intake by P rats while having no effect on alcohol consumption by nondependent controls. Conversely, operant alcohol responding was reduced similarly in dependent and nondependent P rats by naltrexone.

These results confirm a role for brain CRF₁-receptor systems in dependence-induced changes in the reinforcing properties of alcohol, and CRF₁-receptor blockade appears to suppress dependence-induced drinking at lower doses in P rats relative to other rat lines. Therefore, brain CRF₁-receptor systems are important in the regulation of dependence-induced alcohol consumption, whereas brain opioid systems are important in the regulation of basal alcohol consumption by rats.

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