title: The effects of 6-hydroxydopamine lesions of the nucleus accumbens and the mesolimbic dopamine system on oral self-administration of ethanol in the rat.
abstract: Rats readily learn to self-administer ethanol using a procedure where ethanol is introduced in the presence of a sweetener. After gradual removal of the sweetener, sufficient quantities of ethanol are self-administered in non fluid-, non food-deprived rats to produce reliable blood ethanol concentrations. Previous studies using this self-administration model have shown that dopamine receptor antagonists injected systemically or directly into the terminal regions of the mesolimbic dopamine system decrease lever pressing for ethanol, suggesting an important role for dopamine in ethanol reinforcement. The purpose of the present study was to test the hypothesis that the mesolimbic dopamine system is a critical substrate for ethanol reinforcement. Results of this study show that 6-hydroxydopamine (6-OHDA)-induced lesions of the mesolimbic dopamine system, sufficient to produce a 93% depletion of dopamine in the nucleus accumbens, an 85% depletion in the olfactory tubercle, an 82% depletion in the frontal cortex and a 78% depletion in the amygdala, failed to alter ethanol self-administration as measured by the total lever presses. However, the 6-OHDA lesion rats showed an altered pattern of responding for ethanol: an increase in the slope of the regression line of cumulative responses vs. time and an increase in the frequency of responding at inter-response intervals of 4-6 and 6-8 s post 6-OHDA lesion; suggesting that this lesion produced a subtle change in motor or attentional function. The results of this study indicate that while the mesolimbic dopamine system may contribute to the reinforcing actions of ethanol, it is not critical for maintaining ethanol reinforcement.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: S
authors.initials: S
authors.lastname: Rassnick
authors.forename: L
authors.initials: L
authors.lastname: Stinus
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000284:Administration, Oral; D000428:Alcohol Drinking; D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D008032:Limbic System / Q000473:pathology / Q000502:physiology*; D008297:Male; D009043:Motor Activity; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009830:Olfactory Bulb / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012646:Self Administration
chemical_list: D016627:Oxidopamine; D004298:Dopamine