Alcohol drinking induced in the monkey by Tetrahydropapaveroline (THP) infused into the cerebral ventricle

Abstract

In the female macaque monkey acclimated to a primate cchair, Collision cannulae were stereotaxically implanted bilaterally in the lateral cerebral ventricle. The voluntary self-selection of ethyl alcohol versus water was determined repeatedly during a series of 12-day test sequences in which the concentration of the alcohol solution offered to the primate was increased systematically over 12 successive days from 3% to 30%. Following control preference sequences, the dopamine-dopaldehyde condensation product, tetrahydropapaveroline (THP), was infused daily in each monkey's cerebral ventricle (ICV) in a volume of 200–400 μl. THP was dissolved in an artificial CSF, with pH adjusted to3.8 with 0.1 mg/ml ascorbate, and infused in one of ten doses varying from 0.125–400 μg. Each monkey was administered one low and one high dose of the condensation productt throughout each of two successive alcohol preference tests. When THP was infused in doses of less than 2.0 μg, the monkeys' alcohol preference failed to change. However, a marked increase in alcohol intake, in terms of both g/kg/day as well as the proportion of alcohol to water selected, was produced by THP infused ICV in doses of 5.0 to 20.0 μg. Although average intakes in the latter animals were between 4.0 and 5.0 g/kg/day, the monkeys selected certain concentrations of alcohol in amounts of up to 7.0 g/kg/day. The two highest doses of THP, 40.0 and 400.0 μg, inhibited the self-selection of alcohol even when presented in low, non-aversive concentrations in the 3% to 6% range. Overall, these results with the primate corroborate earlier findings in the rat of abnnormal alcohol intake produced by centrally infused THP. They further support the theory that amine-aldehyde metabolites, if present in certain concentrations in the brain, may constitute a causal neurochemical factor in the addictive or otherwise immoderate drinking of alcohol.