Effect of nociceptin on alcohol intake in alcohol preferring rats

The present study investigated the effect of nociceptin (NC). the endogenou s ligand of the opioid-like orphan receptor ORL1, on ethanol intake in gene tically selected Marchigian Sardinian alcohol-preferring (msP) rats. Acute intracerebroventricular (ICV) injection of 250 or 500 ng/rat of NC, just be fore access to 10% ethanol (offered 2 h/day), significantly increased ethan ol intake. Subchronic (7 days) ICV injection of 500 ng/rat of NC, given jus t before access to 10% ethanol (for 30 min/day), resulted in a progressive decrease in ethanol consumption. After the end of NC treatment. rats progre ssively recovered their usual ethanol intake. When NC, 500 or 1000 ng/rat, was tested versus the effect of ethanol in the place conditioning paradigm, NC significantly reduced the increase in time spent in the ethanol-paired compartment after conditioning. This finding suggests that NC reduces the r ewarding properties of ethanol in msP rats; thus, they may respond to the a cute NC administration by increasing their ethanol intake in an attempt to achieve the usual reinforcing effect of ethanol, whereas subchronic NC trea tment may result in extinction of ethanol drinking. The results of the pres ent study suggest that the brain NC mechanisms may represent an interesting target of pharmacological interventions for the treatment of alcoholism.