LOCALIZATION, REGULATION, AND ROLE OF THE DOPAMINE D-3 RECEPTOR ARE DISTINCT FROM THOSE OF THE D-2 RECEPTOR

The phenotypical characterization of neurons bearing the dopamine D-3 receptor in the nucleus accumbens was investigated by in situ hybridiz ation. A large fraction of neurotensin neurons in the ventromedial she ll subdivision of the nucleus accumbens was shown to express D-3 recep tors. Blockade of D-2/D-3 receptors by antipsychotic agents paradoxica lly decreased neurotensin gene expression in these neurons, whereas it enhanced such expression in other striatal areas expressing the D-2 r eceptor. This suggests that D-2 and D-3 receptors mediate opposite act ions of dopamine. In support of this view, low doses of nafadotride, a novel D-3-receptor-preferring antagonist, enhance locomotor activity in rodents, a behavioral response opposite to that obtained with curre nt neuroleptics. The action of D-3-receptor-preferring agonists was ch aracterized by the mitogenic response they elicited in transfected NG 108-15 cells. Finally, gene expression of the D-3 receptor opposes tha t of the D-2 receptor, being decreased by denervation and unaffected b y chronic blockade by neuroleptics.