Alcohol drinking attenuated by sertraline in rats with 6-OHDA or 5,7-DHT lesions of N. accumbens: A caloric response?

The purpose of this study was to elucidate further the role of serotonin (5-HT) in the preference for ethyl alcohol induced in the Sprague-Dawley rat by lesions of the N. accumbens. Following a standard preference test for 3–30% alcohol, dopaminergic or serotonergic neurons in the N. accumbens of the rat were lesioned bilaterally by 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT), respectively. After recovery postoperatively, each rat was offered water and its maximally preferred concentration of alcohol, which ranged from 7% to 11%. Following a 4-day pretest, either the saline control vehicle or the 5-HT reuptake inhibitor, sertraline, was injected subcutaneously in a dose of either 3.0 or 10 mg/kg b.i.d. at 0800 and 2000 h over the next 3 days. Alcohol preference during the injection sequence and for 4 days thereafter was significantly reduced by sertraline in terms of both absolute g/kg and proportion of alcohol to water intakes. Saline was without effect on alcohol drinking. Comparisons of the drinking profiles of serotonergic versus dopaminergic lesioned rats revealed a dose dependent response to sertraline only in the 5,7-DHT lesioned animals. Although sertraline did not alter water drinking, the consumption of food declined significantly during and after its administration with a decline in body weight also observed at the higher dose. These results suggest that in addition to dopaminergic neurons in the N. accumbens, the synaptic activity of 5-HT in this structure contributes to the aberrant drinking of alcohol. However, this interpretation is tempered by the fact that caloric intake was suppressed concomitantly by the drug. Thus the presumed central action of sertraline may not be functionally specific to the reinforcing or other behavioral properties of alcohol.