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 et hanol-induced striatal ascorbic acid release in rats. In the present study the possible role of 5-HT3 receptors in ethanol-induced striatal ascorbic a cid release was investigated in rats using 5-HT3 antagonists ondansetron, D AU 6215 and 5-HT3 agonist 2-methyl-serotonin. Extracellular level of ascorb ic acid in the striatum was deter mined by means of in vivo microdialysis c oupled to HPLC with electrochemical detection. Ethanol (3 g/kg, i.p.) induc ed 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-se rotonin (250 mug/rat, i.c.v.), administered 10 minutes before 0.15 M NaCl o r 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 mug/rat, i.c.v., increased the basal, but did not affect the ethanol-induc ed ascorbic acid release in rat striatum. However, ritanserin (1 mg/kg, s.c .), a 5-HT2 receptor antagonist, and BIMU 8 (40 mug/rat, i.c.v.), a 5-HT4 a gonist, significantly antagonized ethanol-induced ascorbic acid release. Th ese results suggest that 5-HT3 receptors, which form a part of cation chann els, may not be involved in ethanol induced striatal ascorbic acid release.