Alcohol drinking in the rat induced by acute intracerebral infusion of two tetrahydroisoquinolines and a β-carboline

Abstract

Rats of the Sprague-Dawley strain were pre-screened for their preference of alcohol over water with the solutions of alcohol offered increasing systematically over 12 days from 3–30% concentration. Each rat was then surgically prepared with indwelling guide cannulae so that microinfusions of amine condensation products could be made acutely into either the lateral or third cerebral ventricle. At the same hour on each of the 12 days of the preference test sequence, the test compound or cerebrospinal fluid control vehicle was microinfused in a volume of 5.0 μ1 either unilaterally, bilaterally in the lateral ventricles, or directly into the third ventricle. A single infusion once a day into the lateral ventricle of tetrahydropapaveroline (THP) in doses of 0.1–1.0 μg produced an increase in alcohol drinking in this non-preferring strain of rats. The mean proportions of alcohol to water consumed per day over 12 days, as well as the actual intake of alcohol in g/kg per day rose markedly above control levels. THP evoked an ever-rising intake in grams of alcohol as the concentrations of the fluid offered were increased. Several animals drank voluntarily as much as 8.0–10.0 g/kg per day of alcohol during the latter half of the preference sequence when the alcohol offered was in the range 11–30% concentration. Some rats exhibited “wet dog shakes”, exophthalmos, motor impairment, tail stiffness, piloerection, and broad-based walking. When a mixture of tryptoline and THP, or salsolinol and THP, was infused similarly, again alcohol consumption was enhanced significantly in some rats. These results support the hypothesis that a family of amine condensation products acting within limbic forebrain structures mediates the abnormal selection and intake of alcohol. Thus, these compounds may be involved in the etiology of the addictive state.