Stimulation of brain dopamine autoreceptors by remoxipride administration in reserpine-treated male rats

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Abstract
Male Sprague-Dawley rats were treated subcutaneously with reserpine (5 mg kg−1, — 18 h) and with the aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine) (100 mg kg−1 -30 min). Remoxipride 0 -8, 3 -2 or 12 -8 mg kg−1 was administered subcutaneously at -50 min. Immediately following decapitation (0 h), the ventral striatum and the anterior neocortex were dissected. Dopa and 5-hydroxytryptophan accumulation in these brain areas were analysed by HPLC with electrochemical detection. Reserpine produced a marked increase in striatal and neocortical dopa accumulation, in comparison with glucose vehicle + NSD-1015-treated controls, and this increase was dose-dependently antagonized by remoxipride treatment. Thus, together with demonstrated dopamine receptor antagonist actions in intact animals, remoxipride behaves as a mixed dopamine receptor agonist-antagonist. Such properties could contribute to the favourable endocrine and extrapyramidal side effect profile of remoxipride as an antipsychotic agent.

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