MEDIAN AND DORSAL RAPHE INJECTIONS OF THE 5-HT1A AGONIST, 8-OH-DPAT, AND THE GABA(A), AGONIST, MUSCIMOL, INCREASE VOLUNTARY ETHANOL INTAKE IN WISTAR RATS

Low doses of the selective 5-HT1A agonist 8-OH-DPAT increase ethanol intake in a limited access paradigm following peripheral injection. This may be due to a reduction in 5-HT neurotransmission following activation of raphe somatodendritic autoreceptors. In order to test this hypothesis, and to determine the effects of selective reductions in raphe 5-HT activity, experiments examined the effects of injecting 8-OH-DPAT into the dorsal raphe (0, 0.02, 0.1, 1 and 2.5 mu g) or the median raphe (0, 0.1, 1 and 5 mu g) in rats trained to drink 12% ethanol for 40 min each day. The effects of the GABA(A) agonist, muscimol, on ethanol intake were also examined. Ethanol intake was increased at the highest dose of 8-OH-DPAT following injection into either site, with no change in water intake. Thus, the effects of 8-OH-DPAT are selective for ethanol. The selective 5-HT1A antagonist, (+/-)-WAY100135 (0.3, 1 and 3 mg/kg), blocked the effect of 8-OH-DPAT, showing that activation of 5-HT1A receptors underlies the ethanol drinking induced by 8-OH-DPAT. These results are consistent with the idea that reduced 5-HT function increases ethanol intake. Several behavioural mechanisms for this effect are discussed. Muscimol (50-100 ng) also increased ethanol drinking. Following injection into the median raphe, muscimol also stimulated water intake. These effects are probably due to non-specific behavioural activation induced by this treatment. However, the effect of muscimol in the dorsal raphe was specific for ethanol since water intake was not altered. Together, these results imply that serotonergic elements within the dorsal and median raphe, as well as non-serotonergic elements within the dorsal raphe may represent important neurochemical systems controlling ethanol drinking.