PROMINENCE OF THE DOPAMINE D2 SHORT ISOFORM IN DOPAMINERGIC PATHWAYS

As a result of alternative splicing, the D2 gene of the dopamine recep tor family exists in two isoforms. The D2 long is characterized by the insertion of 29 amino acids in the third cytoplasmic loop, which is a bsent in the short isoform. We have produced subtype-specific antibodi es against both the D2 short and D2 long isoforms and found a unique c ompartmentalization between these two isoforms in the primate brain. T he D2 short predominates in the cell bodies and projection axons of th e dopaminergic cell groups of the mesencephalon and hypothalamus, wher eas the D2 long is more strongly expressed by neurons in the striatum and nucleus accumbens, structures targeted by dopaminergic fibers. The se results show that the splice variants of the dopamine D2 receptor a re differentially distributed and possess distinct functions. The stra tegic localization of the D2 short isoform in dopaminergic cell bodies and a.axons strongly suggests that this isoform is the likely dopamin e autoreceptor, whereas the D2 long isoform is primarily a postsynapti c receptor.