SEROTONIN-3 RECEPTOR AND ETHANOL-STIMULATED SOMATODENDRITIC DOPAMINE RELEASE

The effects of local application of the 5-HT3 receptor agonist, 1-(m-c hlorophenyl)-biguanide (CPBG), and IP administration of ethanol on the extracellular levels of dopamine (DA) in the ventral tegmental area ( VTA) were studied using in vivo microdialysis. Adult female Wistar rat s were implanted with microdialysis probes in the VTA at least 24 h be fore each experiment. Stable extracellular levels of DA (101 +/- 9 fmo l/20 min) were established before initiating the experiments. Applicat ion of 10-250 mu M CPBG through the microdialysis probe dose-dependent ly enhanced the extracellular concentrations of DA but did not alter t he levels of either 3,4-dihydroxyphenylacetic acid or homovanillic aci d in the dialysate. The effects of CPBG were reversible and dependent upon Ca2+. Co-perfusion with the 5-HT3 receptor antagonist, 3-tropanyl -indole-3-carboxylate (ICS 205-930), inhibited the effects of CPBG on enhancing extracellular DA levels. The IP administration of 2 g/kg eth anol significantly (p < 0.005) enhanced the levels of DA to 150% of ba seline values; this ethanol-induced increase was prevented by local pe rfusion with 100 mu M ICS 205-930. These results suggest that 5-HT3 re ceptors in the VTA are involved in regulating the somatodendritic rele ase of DA and in mediating the stimulatory effects of ethanol on this neuronal system. Copyright (C) 1996 Elsevier Science Inc.