The dopamine D₃ receptor is a member of the D2 family of dopamine receptors. Several investigators have suggested that D₃ receptors are involved in the regulation of locomotion,¹ in the pathophysiology of schizophrenia,² and in drug abuse.³

Dopamine enhances basal and stimulus evoked release of arachidonic acid, as well as the production of one of its metabolites, prostaglandin E₂ (PGE₂), in CHO (Chinese hamster ovary) cells transfected with the D₂ receptor.^4–6 In contrast, dopamine does not influence basal arachidonic acid release^7–9 but inhibits stimulus evoked release in cells transfected with the rat D₃ receptor.¹⁰ On the other hand, with respect to cAMP production, the effect of dopamine is similar in CHO cells transfected with either D₂ or D₃ receptors, both receptor subtypes mediating a reduction in forskolin induced cAMP formation.^11,12

A single nucleotide polymorphism (SNP) in the first exon of the dopamine D₃ receptor gene, the ser9gly polymorphism, leads to a serine to glycine amino acid substitution in the N-terminal extracellular domain of the receptor protein.¹³ An association between this polymorphism and schizophrenia has been suggested, but also questioned,^14,15 a meta-analysis suggesting the effect to be small but real in white subjects.¹⁶ Other investigators have suggested that the gly-9 allele may be associated with an increased risk of developing antipsychotic induced tardive dyskinesia rather than with schizophrenia per se¹⁷; this finding also gained support from a report containing both pooled analyses of original data and a meta-analysis,¹⁸ and also from a recent primate study¹⁹ (see also a recent report by Lohmueller and coworkers²⁰). In addition, the ser9gly polymorphism has been reported to be associated with therapeutic response to atypical antipsychotic agents, …