SEROTONIN POTENTIATES ETHANOL-INDUCED EXCITATION OF VENTRAL TEGMENTALAREA NEURONS IN BRAIN-SLICES FROM 3 DIFFERENT RAT STRAINS

Neurons of the ventral tegmental area of Tsai (VTA) are important in m ediation of the rewarding effects of drugs of abuse, including ethanol . We have demonstrated previously that ethanol excites neurons of the VTA recorded in a brain slice preparation. In the present study, we te sted the interaction between serotonin and ethanol on putative dopamin e neurons of the VTA. As reported previously, ethanol (20-160 mM) exci ted VTA neurons in a concentration-dependent manner. Serotonin (1-50 m u M) produced only minor increases or decreases of the firing rate. In the presence of serotonin, the potency of ethanol was increased signi ficantly. This potentiation of ethanol excitation by serotonin was see n in VTA slices taken from Sprague-Dawley, Fischer 344 and Lewis rats. The effect of 160 mM ethanol on VTA neurons from Fischer 344 rats, fo r example, was increased from 38.5 +/- 6.1% before serotonin to 77.4 /- 16.7% after administration of 10 mu M serotonin. Two serotonergic a gonists, (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride and cr-me thylserotonin, also potentiated the ethanol-induced excitation. The ac tion of serotonin to increase the potency of ethanol to excite VTA neu rons may be an important factor in the rewarding effects of ethanol, a nd might be-exploited to develop effective pharmacotherapeutic agents for the treatment of alcohol craving.