The present study investigated the effect of nociceptin (NC), the endogenous ligand of the opioid-like orphan receptor ORL1, on ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Acute intracerebroventricular (i.c.v.) injection of 250 or 500 ng/rat of NC, just before access to 10% ethanol (offered 2 h/day), significantly increased ethanol intake. Subchronic (7 days) i.c.v. injection of 500 ng/rat of NC, given just before access to 10% ethanol (for 30 min/day), resulted in a progressive decrease in ethanol consumption. After the end of NC treatment, rats progressively 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 rewarding properties of ethanol in msP rats; thus, they may respond to the acute NC administration by increasing their ethanol intake in an attempt to achieve the usual reinforcing effect of ethanol, whereas subchronic NC treatment may result in extinction of ethanol drinking. The results of the present study suggest that the brain NC mechanisms may represent an interesting target of pharmacological interventions for the treatment of alcoholism.
The present results provide evidence for an antidepressant-like action of ethanol in sP and msP rats and suggest that this action may contribute to sustain their high ethanol drinking.
The study of the biological mechanisms of ethanol reward has greatly suffered from problems to obtain ethanol-induced conditioned place preference (CPP) in rats. In the present study, CPP was obtained in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, derived from Sardinian alcohol-preferring rats, following intragastric (IG) ethanol administration by means of a permanent IG catheter, but not after intraperitoneal (IP) injection or IG gavage. Rats with permanent IG catheter, received IG administration of 0.35, 0.7, 1.5 or 2.8 g/kg ethanol, as a 10% v/v solution. In ethanol-experienced rats 0.7 or 1.5, but not 0.35 or 2.8 g/kg ethanol significantly increased in comparison to controls the time spent in the ethanol-associated previously non-preferred compartment, which became preferred in the post-conditioning test. In ethanol-naive rats, only 0.7 g/kg ethanol significantly increased the time spent in the ethanol-associated compartment. On the other hand, no effect was observed in alcohol-experienced rats following IG gavage, or IP injection of 0.35, 0.7 or 1.5 g/kg ethanol. The present results provide evidence that ethanol possesses postingestive rewarding properties in msP rats, and that it can reliably induce CPP in them, provided that an appropriate method of administration is adopted.
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