Naloxone alters alcohol drinking induced in the rat by tetrahydropapaveroline (THP) infused ICV

Abstract

In male rats of the Sprague-Dawley or Long-Evans strain, intracerebroventricular (ICV) cannulae were implanted permanently using stereotaxic techniques. Tetrahydropapaveroline (THP) was infused ICV for up to 14 days either chronically around the clock or acutely once per day in doses previously found to induce an abnormally high intake of alcohol. During these periods, alcohol preference for individual rats was determined by a self-selection procedure in which the concentration of alcohol was increased from 3 to 30% on each day of a 12-day interval. Those rats which displayed a substantial increase in their intake of alcohol were selected for naloxone treatment and subsequently assigned a fixed concentration of alcohol at which maximum consumption occurred. Naloxone was administered subcutaneously two to six times per day for three consecutive days in total daily doses ranging from 1.5 to 3.0 mg/kg. Each rat served as its own control and was given 0.9% saline isovolumetrically according to the same temporal schedule. Naloxone generally suppressed alcohol intake in animals by 20% to 45%, but the reduction in drinking depended upon the injection regimen as well as the prior level of alcohol consumption. In “high drinking” rats, the mean alcohol intake of 6.2 g/kg/day was reduced to 3.7 g/kg/day by naloxone whereas in “low drinkers” the mean intake of 3.5 g/kg/day was suppressed to 2.8 g/kg/day by the opiate antagonist. These results further support the suggestion of a possible opiate receptor link in the pathogenesis and maintenance of aberrant drinking of alcohol, the mechanism of which may involve the endogenous action of an amine-aldehyde condensation product in the brain.