In vivo binding of 3H-pimozide in mouse striatum: Effects of dopamine agonists and antagonists

Several lines of evidence indicate that the i.v. injection of ³H-pimozide results in a specific in vivo binding of the neuroleptic to dopaminergic receptors.First, ³H-pimozide is preferentially accumulated in the striatum as compared to non-dopaminergic structures like the cerebellum. Second, the selective accumulation of ³H-pimozide is prevented by prior administration of various neuroleptics as well as by apomorphine. Moreover, doses of antagonists which prevent this accumulation were identical to those which lead to an increased striatal HVA level. Third, ³H-pimozide accumulation is not modified by the administration of a variety of non-dopaminergic agents.However, ³H-pimozide binding is not prevented either by indirect dopamine agonists and is even greatly increased by d-amphetamine at high doses. The possibility that direct or indirect dopamine agonists may favour the binding of the antagonist through a modification of receptor sites is discussed.