Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens

Abstract

The present study was undertaken to examine the involvement of activation of 5-HT 3 receptors in the rat nucleus accumbens (Acb) on the effects of ethanol-induced increases of dopamine (DA) using the selective agonist 1-(m-chlorophenyl)-biguanide (CPBG). Perfusion of CPBG through the microdialysis probe concentration-dependently (3.3–100 μM) enhanced the extracellular levels of DA in the Acb. Extracellular DA concentrations increased as high as 1000% of baseline. The CPBG-induced increases in DA levels were Ca ++ dependent and inhibited by local perfusion with the 5-HT 3 antagonist ICS 205-930 (100 μM). In addition, CPBG at high concentrations caused significant decreases in the extracellular levels of DA metabolites. Intraperitoneal (IP) injection of 1 g/ kg ethanol produced no changes in extracellular DA levels in the Acb; coadministration of 1 g/kg ethanol (IP) and 5 μM CPBG (local) produced increases equal to 5 μM CPBG alone. Administration of 2 g/kg ethanol (IP) alone enhanced extracellular DA levels by ~60% above baseline, whereas local perfusion of 5 μM CPBG alone produced an increase of ~100% above baseline. The coadministration of 2 g/kg ethanol (IP) and 5 μM CPBG (local) enhanced DA levels by approximately 170% above baseline; this apparent additive enhancement was almost completely prevented when 100 μM ICS 205–930 was locally coperfused. Local administration of 3.3–100 μM CPBG did not alter the extracellular levels of serotonin or 5-hydroxyindoleacetic acid. The results support an involvement of 5-HT 3 receptors in regulating DA release in the Acb, and also in mediating ethanol-induced DA release. However, the in vivo interaction of ethanol and 5-HT at the 5-HT 3 receptor within the Acb is clearly not synergistic.