Ethanol drinking following 6-OHDA lesions of nucleus accumbens and tuberculum olfactorium of the rat.

Abstract

Previous studies have shown that lesions of the dopaminergic system in the brain produced by an intracerebroventricular injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), evoke significant changes in ethanol drinking. In the present experiments, dopaminergic systems of Sprague-Dawley rats were lesioned by 6-OHDA infused into either the tuberculum olfactorium or nucleus accumbens, two of the structures implicated in drug-related reinforcement. Prior to the lesion and immediately thereafter, tests for ethanol preference were undertaken in which water was offered in a self-selection situation together with ethanol which was increased in concentration from 3-30% over a 10-day interval. Following the circumscribed ablation of dopaminergic neurons within either the N. accumbens or tuberculum olfactorium, preference for ethanol increased significantly with absolute intakes exceeding 4.0 g/kg at the 7% concentration during the first postlesion drinking test. During the second postlesion preference test, the mean consumption of ethanol exceeded 6.0 g/kg at the 11% concentration and 4.0 to 5.0 g/kg at the 20 and 30 percent concentrations offered to the rats. When adjacent areas just dorsal or lateral to these structures were lesioned by 6-OHDA, no significant change in consumption of ethanol occurred. Thus, it is envisaged that one of the functional roles for the dopaminergic neurons of the N. accumbens and tuberculum olfactorium is to regulate the craving for a drug with addictive liability such as ethanol. As a result of an impairment of normal function of dopamine receptors or a perturbation in the release of this catecholaminergic neurotransmitter, ethanol becomes reinforcing upon repeated exposure. Thus, an addictive-like state consequently ensues. Finally, it is envisaged that the control mechanism underlying the function of the dopaminergic neurons in the medial-basal forebrain is functionally disinhibited in individuals that consume ethanol to the point of abuse.