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  • Title: Dopamine receptor subtypes: differential regulation after 8 months treatment with antipsychotic drugs.
    Author: Florijn WJ, Tarazi FI, Creese I.
    Journal: J Pharmacol Exp Ther; 1997 Feb; 280(2):561-9. PubMed ID: 9023264.
    Abstract:
    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 Dl-like or D3 dopamine receptor subtype binding.
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