The D3 receptor and its relevance in psychiatry

A large fraction of neurotensin neurons in the ventromedial shell subdivision of nucleus accumbens express D3 receptors. Blockade of D2/D3 receptors by antipsychotic agents paradoxically decreases neurotensin gene expression in these neurons whereas it enhances it in other striatal areas expressing the D2 receptor. This suggests that D2 and D3 receptors mediate opposite actions of dopamine. In support of this view low doses of nafadotride, a novel D3 receptor-preferring antagonist, enhances locomotor activity in rodents, a behavioral response opposite to that of current neuroleptics. The action of D3 receptor-preferring agonists was characterized by the mitogenic response they elicit in transfected NG 108-15 cells. Finally, gene expression of the D3 receptor is in opposition to that of the D2 receptor, being decreased by denervation and unaffected by chronic blockade by neuroleptics.