S. Rassnick et al., THE EFFECTS OF 6-HYDROXYDOPAMINE LESIONS OF THE NUCLEUS-ACCUMBENS ANDTHE MESOLIMBIC DOPAMINE SYSTEM ON ORAL SELF-ADMINISTRATION OF ETHANOLIN THE RAT, Brain research, 623(1), 1993, pp. 16-24
Rats readily learn to self-administer ethanol using a procedure where
ethanol is introduced in the presence of a sweetener. After gradual re
moval of the sweetener, sufficient quantities of ethanol are self-admi
nistered in non fluid-, non food-deprived rats to produce reliable blo
od ethanol concentrations. Previous studies using this self-administra
tion model have shown that dopamine receptor antagonists injected syst
emically or directly into the terminal regions of the mesolimbic dopam
ine system decrease lever pressing for ethanol, suggesting an importan
t role for dopamine in ethanol reinforcement. The purpose of the prese
nt study was to test the hypothesis that the mesolimbic dopamine syste
m is a critical substrate for ethanol reinforcement. Results of this s
tudy show that 6-hydroxydopamine (6-OHDA)-induced lesions of the mesol
imbic dopamine system, sufficient to produce a 93% depletion of dopami
ne in the nucleus accumbens, an 85% depletion in the olfactory tubercl
e, an 82% depletion in the frontal cortex and a 78% depletion in the a
mygdala, failed to alter ethanol self-administration as measured by th
e total lever presses. However, the 6-OHDA lesion Tats showed an alter
ed pattern of responding for ethanol: an increase in the slope of the
regression line of cumulative responses vs. time and an increase in th
e 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 cha
nge in motor or attentional function. The results of this study indica
te that while the mesolimbic dopamine system may contribute to the rei
nforcing actions of ethanol, it is not critical for maintaining ethano
l reinforcement.