DIFFERENTIAL REGULATION OF DOPAMINE-RECEPTORS AFTER CHRONIC TYPICAL AND ATYPICAL ANTIPSYCHOTIC DRUG-TREATMENT

Changes in dopamine receptor subtype binding in different brain region s were examined after 28 days treatment of rats with haloperidol, racl opride, clozapine or SCH23390 using in vitro receptor autoradiography. [H-3]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D- 3 receptors was not changed in any brain region by any of the drug tre atments. [H-3]SCH23390 was only increased by chronic SCH23390 treatmen t. Haloperidol significantly increased [H-3]nemonapride and [H-3]spipe rone like receptors in the caudate-putamen. In contrast, haloperidol c aused a small, significant increase in [H-3]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesse r extent [H-3]nemonapride and [H-3]spiperone binding in caudate-putame n, whereas it did not affect [H-3]raclopride binding. Clozapine did no t significantly change D-2-like striatal binding of [H-3]nemonapride, [H-3]spiperone or [H-3]raclopride. The differences in radioligand bind ing suggest that [H-3]nemonapride and [H-3]spiperone may be binding to additional subsets of dopamine D-2-like receptors (including D-4-like receptors) that are not recognized by [H-3]raclopride, which has high affinity for D-2 and D-3 receptors only. Quantification of [H-3]nemon apride or [H-3]spiperone binding in the presence of 300 nM raclopride (to block D-2 and D-3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D-4-like receptors in the caudate-putamen using either radioligand. These results suggest that D-4-like receptor s may be a common site of action of both typical and atypical antipsyc hotics. (C) 1997 IBRO. Published by Elsevier Science Ltd.