Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats
Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol-seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p<0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p<0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p<0.05) densities of 5-HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5-HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol. The IP administration of agents which can increase the physiologically active pool of 5-HT (e.g., fluoxetine, an uptake inhibitor; fenfluramine, a releaser; and D,L-5-hydroxytryptophan, an immediate precursor) or which can mimic 5-HT (e.g., 5-HT1 and 5-HT2 agonists) all significantly decreased the volitional alcohol intake of the high alcohol-seeking rats. Similarly, the IP administration of a DA uptake inhibitor, DA releaser or D2 agonist also reduced the volitional oral intake of alcohol by the P line of rats. In addition, the consumption of alcohol by the P line of rats is reduced by IP administration of Ro 15-4513, an inverse agonist at the GABAA-benzodiazepine-Cl- receptor complex. Overall, the data suggest that abnormalities exist in certain 5-HT, DA and GABA systems in the CNS of P and HAD rats and that these abnormal transmitter systems may be major underlying biological factors contributing to their high alcohol-seeking characteristics. A hypothesis is offered to explain the involvement of the 5-HT, DA and GABA systems of the nucleus accumbens in regulating alcohol drinking of the selectively bred P and HAD lines of rats. © 1990.
McBride, WJ; Murphy, JM; Lumeng, L; Li, TK
Volume / Issue
Start / End Page
International Standard Serial Number (ISSN)