Dopamine D 3 receptor mRNA and binding sites in human brain

Abstract

Dopamine D 3 receptors (Sokoloff et al., 1990) have been shown to be related to dopamine D 2 receptors and have been suggested to play a role in mediating the antipsychotic effects of neuroleptics. So far studies on the expression of D 3 mRNA and of binding sites with pharmacological characteristics of D 3 receptors have been restricted to rat brain. Using in situ hybridization histochemistry, we demonstrate that D 3 mRNAs are enriched in human n. accumbens and in the islands of Calleja. In addition, D 3 mRNA was detected at very low levels in anterior caudate and putamen with a rostro-caudally decreasing gradient and in hypothalamic mammillary nuclei. In receptor autoradiographic binding studies, the islands of Calleja were found to be labeled by [ 125I]iodosulpride and [ 3H]CV 205 502 but not by [ 3H]raclopride and [ 3H]YM 09151-2. Pharmacological analysis of binding of the D 2/D 3 ligand [ 3]H]CV 205 502 in n. accumbens and caudate-putamen is consistent with the presence of D 3 receptor sites in ventral striatum. Overall distribution and pharmacology of D3 sites in human and rat brain appear to be similar. Presence and distribution of D 3 receptors in human brain are compatible with the notion that D 3 receptors might be involved in mediating the clinical effects of antipsychotics.