POSSIBILITY OF 5-HT3 RECEPTOR INVOLVEMENT IN ALCOHOL DEPENDENCE - A MICRODIALYSIS STUDY OF NUCLEUS-ACCUMBENS DOPAMINE AND SEROTONIN RELEASEIN RATS WITH CHRONIC ALCOHOL-CONSUMPTION

The present study was performed to examine the involvement of serotoni n-3 (5-HT3) receptors in the rat nucleus accumbens (ACC) in alcohol de pendence. In alcohol-treated rats, perfusion of 40 mM K+ and 100 mM et hanol (EtOH) through the microdialysis probe increased the extracellul ar levels of ACC dopamine (DA), compared with controls. Perfusion of t he serotonin (5-HT) uptake inhibitor sert-larine enhanced the extracel lular levels of ACC 5-HT in both groups. Increased 5-HT availability i n the synaptic clefts on the ACC further activated ACC DA release in t he alcohol-treated rats, in comparison with controls. In the final exp eriments, perfusion of the 5.0 mu M 5-HT3 receptor agonist 2-methyl-5- HT (2-Me-5-HT) through the microdialysis probe enhanced the extracellu lar levels of ACC DA. Magnitude of 2-Me-5-HT-induced DA release was si gnificantly higher in alcohol-treated rats than in controls. On the ot her hand, 40 mM K+- and 100 mM EtOH-induced extracellular 5-HT release in alcohol-treated rats were markedly inhibited. These results show t hat (1) chronic alcohol intake increases the sensitivity of 5-HT3 rece ptors, (2) 5-HT3 receptors regulate DA release in the ACC, (3) the dop aminergic neuronal systems associated with 5-HT3 ionophore in the ACC were upregulated after chronic alcohol exposure, and (4) chronic alcoh ol intake desensitizes the serotonergic neuronal systems in rat ACC. T hese findings suggest that neurochemical functions of 5-HT3 receptors in regulating DA release in the ACC after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original p roperties in processing alcohol tolerance and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors.