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Vol. 280, Issue 2, 561-569, 1997

Dopamine Receptor Subtypes: Differential Regulation after 8 Months Treatment with Antipsychotic Drugs1

Wouter J. Florijn2, Frank I. Tarazi3 and Ian Creese

Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Ave., Newark, New Jersey

Regulation of dopamine receptor subtypes was determined after long-term (8 mo) administration of typical and atypical antipsychotic drugs using 3H-nemonapride, 3H-raclopride, 3H-spiperone, 3H-7-hydroxy-N,N-di-n-propyl-2-aminotetralin, 3H-SCH23390 and 125I-sulpiride in vitro receptor autoradiography. Drug-induced receptor upregulation was remarkably different across the various D2-like receptor radioligands. Chronic haloperidol treatment resulted in a strong increase in 3H-nemonapride, 3H-spiperone and 125I-sulpiride binding to striatal areas, whereas 3H-raclopride binding was marginally affected. Raclopride treatment elevated striatal binding of 3H-nemonapride and 3H-spiperone to a lesser extent, and did not alter 3H-raclopride binding. Clozapine treatment did not affect the binding of the tritiated radioligands. These differences suggest that 3H-nemonapride and 3H-spiperone are binding to an additional subset of D2-like receptors, not recognized by 3H-raclopride. 3H-Nemonapride binding in the presence of 300 nM raclopride uncovered a striatal binding site (designated as D4-like receptor), that was up-regulated after chronic haloperidol, raclopride and clozapine treatment. The 125I-sulpiride binding sites in the prefrontal cortex were also up-regulated by the three antipsychotics. In contrast, 3H-spiperone binding sites were down-regulated in the prefrontal and dorsolateral cortical area. Chronic antipsychotic treatment did not affect D1-like or D3 dopamine receptor subtype binding.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


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