Rationale: The ventral tegmental area (VTA) mediates the local stimulating effects of ethanol (EtOH) in a region-dependent manner, with EtOH administration in the posterior but not anterior VTA stimulating the mesolimbic system. The serotonin-3 (5-HT3) receptor has been involved in the effects of EtOH on the mesolimbic system. Objectives: The current study tested the hypothesis that EtOH would stimulate mesopallidal and mesocortical dopamine neurons in the posterior but not anterior VTA and that the stimulating effects of EtOH in the VTA would involve activation of local 5-HT3 receptors. Methods: Wistar female rats were surgically implanted with two cannulae, one in one sub-region of the VTA for microinjection and the other in the ventral pallidum (VP) or medial prefrontal cortex (mPFC) for microdialysis. Artificial cerebrospinal fluid or EtOH (200 mg%; 44 mM) was microinjected in the anterior or posterior VTA, and extracellular dopamine was measured in the VP or mPFC with microdialysis-HPLC. Results: EtOH injections in the posterior but not anterior VTA significantly increased extracellular dopamine levels in the VP and mPFC. Co-injections of the 5-HT3 receptor antagonist ICS-205,930 with EtOH in the posterior VTA significantly reduced the effects of EtOH on extracellular dopamine levels in the VP and mPFC. Conclusions: The results indicate that posterior VTA dopamine neurons projecting to the VP and mPFC are stimulated by local administration of EtOH and that the local stimulating effects of EtOH are mediated, at least in part, by 5-HT3 receptors.
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