THE D-3 RECEPTOR AND ITS RELEVANCE IN PSYCHIATRY

A large fraction of neurotensin neurons in the ventromedial shell subd ivision of nucleus accumbens express D-3 receptors. Blockade of D-2/D- 3 receptors by antipsychotic agents paradoxically decreases neurotensi n gene expression in these neurons whereas it enhances it in other str iatal areas expressing the D-2 receptor. This suggests that D-2 and D- 3 receptors mediate opposite actions of dopamine. In support of this v iew low doses of nafadotride, a novel D-3 receptor-preferring antagoni st, enhances locomotor activity in rodents, a behavioral response oppo site to that of current neuroleptics. The action of D-3 receptor-prefe rring agonists was characterized by the mitogenic response they elicit in transfected NG 108-15 cells. Finally, gene expression of the D-3 r eceptor is in opposition to that of the D-2 receptor, being decreased by denervation and unaffected by chronic blockade by neuroleptics.