Failure of 5-HT₃ receptors in regulation of ethanol-induced ascorbic acid release in rat striatum

Previous studies have shown that the serotonergic system was involved in ethanol-induced striatal ascorbic acid release in rats. In the present study the possible role of 5-HT₃ receptors in ethanol-induced striatal ascorbic acid release was investigated in rats using 5-HT₃ antagonists ondansetron, DAU 6215 and 5-HT₃ agonist 2-methyl-serotonin. Extracellular level of ascorbic acid in the striatum was determined by means of in vivo microdialysis coupled to HPLC with electrochemical detection. Ethanol (3 g/kg, i.p.) induced a significant increase in ascorbic acid release. Ondansetron (0.2 and 2.0 mg/kg, i.p.), DAU 6215 (0.06, 0.12 and 0.24 mg/kg, i.p.) and 2-methyl-serotonin (250 μg/rat, i.c.v.), administered 10 minutes before 0.15 M NaCl or ethanol (3 g/kg, i.p.), affect neither the basal nor the ethanol-induced ascorbic acid release in rat striatum. 2-Methyl-serotonin, at a dose of 500 μg/rat, i.c.v., increased the basal, but did not affect the ethanol-induced ascorbic acid release in rat striatum. However, ritanserin (1 mg/kg, s.c.), a 5-HT₂ receptor antagonist, and BIMU 8 (40 μg/rat, i.c.v.), a 5-HT₄ agonist, significantly antagonized ethanol-induced ascorbic acid release. These results suggest that 5-HT₃ receptors, which form a part of cation channels, may not be involved in ethanol-induced striatal ascorbic acid release.