Antagonism by naltrexone of voluntary alcohol selection in the chronically drinking macaque monkey

An opiate receptor antagonist can reduce excessive alcohol drinking in the rat previously given intracerebroventricular (ICV) infusions of a tetrahydroisoquinoline. Recently, it was found that cerebrospinal fluid (CSF) obtained from volunteers or human patients and subsequently injected ICV in macaque monkeys markedly alters the voluntary consumption of ethyl alcohol in certain of these primates. The purpose of the present study was to determine whether an opioid antagonist would affect the pattern of alcohol intake in selected monkeys which drank excessive amounts of alcohol. Initially, the preferred concentration of alcohol was determined individually for each monkey which consistently drank from 3.0-6.0 g/kg alcohol per day. Subsequently, the single concentration, which ranged from 5-15%, was offered together with water during three consecutive periods as follows: (1) 4-day control baseline period; (2) a 3-day interval during which a saline control vehicle or 0.6 or 1.2 mg/kg naltrexone was administered subcutaneously at 0900 and 1700 hours; and (3) a final 4-day post-injection period during which the alcohol-water preference test was continued. The results showed that both doses of naltrexone significantly attenuated voluntary alcohol drinking up to 60% of the baseline intake during the 3 days of its administration. In two monkeys, alcohol drinking continued to be suppressed up to 50% of basal intake during all or a part of the 4-day post-naltrexone interval. These findings suggest that an opiate receptor mechanism in the brain could be partially involved in the action of the chemical constituents of the human's CSF which serve to induce an abnormally high intake of alcohol in the infra-human primate.