Ethanol and Mesolimbic Serotonin/Dopamine Interactions Via 5-HT1B Receptors

Abstract

Abstract : The purpose was to investigate whether activation of 5-HT1B receptors within the ventral tegmental area (VTA) facilitated dopamine (DA) transmission in the ipsilateral nucleus accumbens (NACC) and potentiated ethanol-induced increases in NACC DA by 5- HT1B receptor-mediated GABA mechanisms. The data derived from microdialysis studies performed in rats and 5-HT1B receptor knockout mice, and those obtained from superfusion experiments consistently showed that activation of VTA 5-HT1B receptors facilitated mesolimbic DA transmission and enhanced the stimulatory effects of ethanol on mesolimbic DA neurons. These enhancements may be a consequence of additive effects resulting from indirect disinhibition of VTA DA neurons due to the receptor activation-induced inhibition of VTA GABA release. Moreover, the results showed that blockade of VTA 5-HT1B receptors attenuated ethanol-induced increases in mesolimbic DA transmission, suggesting the involvement of the receptor activation in mediating ethanol's DA activating effects. However, VTA GABA may not be involved in this 5-HT1B receptor-mediated effect since the data from in vivo and in vitro experiments showed that ethanol did not affect VTA GABA transmission. The data also showed that ethanol, when directly applied to VTA slices, increased somato-dendritic DA release, suggesting that the stimulatory effects of ethanol on VTA DA neurons observed in vivo may be associated, at least in part, with its direct actions within the VTA. Our data may explain in part why 5-HT1B receptors have been reported to be associated with alcohol abuse in both human genetics and in animal models, and to play a role in regulating alcohol voluntary intakes.