Abstract

The in vivo brain microdialysis technique has been used to study the ability of itasetron, [DAU 6215, (3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide hydrochloride], a novel 5-hydroxytryptamine3 (5-HT3)-receptor antagonist, to antagonize the effect of the sigma-agonist (+)-N-Allylnormetazocine (SKF 10,047) in inducing the release of dopamine from mesolimbic and nigrostriatal dopaminergic neurons, in comparison with haloperidol and clozapine. SKF 10,047 caused a dose-dependent increase in the release of endogenous dopamine preferentially from the nucleus accumbens septi with respect to the corpus striatum of the rat, the time to peak being 60 min from its administration. Itasetron (1-30 micrograms/kg s.c. given 45 min before SKF 10,047 5 mg/kg s.c.) dose dependently antagonized the SKF 10,047 response in the nucleus accumbens septi and not in the corpus striatum, without inducing by itself changes of basal DA output in either area at these doses. Another selective 5-HT3 receptor antagonist, ondansetron, at the dose of 10 micrograms/kg s.c., like itasetron, blocked the SKF 10,047-induced release of dopamine. At the dose of 100 micrograms/kg s.c., both itasetron and ondansetron failed to modify the effect of SKF 10,047 and increased DA release per se in the nucleus accumbens septi.