EVIDENCE THAT GABA(A) BUT NOT GABA(B) RECEPTOR ACTIVATION IN THE DORSAL RAPHE NUCLEUS MODULATES ETHANOL INTAKE IN WISTAR RATS

Injection of the GABA(A) agonist muscimol into the dorsal raphe nucleu s produces a marked and selective increase in voluntary ethanol intake . The purpose of the present study was threefold: first, to demonstrat e that the effect of muscimol on ethanol consumption is mediated by GA BA(A) receptors; secondly, to test the generalizability of this effect by examining the effects of another GABA(A) agonist, THIP on ethanol drinking; and finally, to examine whether GABA(B) receptors within the dorsal raphe also play a role in modifying voluntary ethanol consumpt ion under the same experimental conditions. Rats were trained to drink a 12% ethanol solution in a limited access paradigm with water concur rently available. Muscimol (50 ng) injected into the dorsal raphe enha nced ethanol intake by at least 100%. Peripheral administration of the GABA(A) antagonist bicuculline (4 mg/kg), but not the 5-HT1A antagoni st(+)-WAY100135 (1 and 3 mg/kg), antagonized the stimulatory effect of muscimol at a dose which, when administered alone, did not alter etha nol intake. This supports the suggestion that the effect of muscimol i s mediated via GABA(A) receptors. This conclusion was further supporte d by the finding that another GABA(A) agonist, THIP (500 ng), also sel ectively increased ethanol intake in this paradigm. Injection of bicuc ulline (60 ng) into the dorsal raphe reduced ethanol intake, but also appeared to reduce water intake. Finally, intra-dorsal raphe injection of the GABA(B) agonist baclofen (62.5 and 125 ng) did not produce any change in ethanol or water consumption. Together, these findings sugg est that enhancement of GABAergic activity in the dorsal raphe increas ed voluntary ethanol intake via activation of GABA(A) but not GABA(B) receptors.