title: Chronic haloperidol affects striatal D2-dopamine receptor reappearance after irreversible receptor blockade.
abstract: The time course of recovery of [3H]spiperone binding in the rat striatum after administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was studied in chronically haloperidol-treated rats (0.5 mg/kg, i.p., twice a day for two weeks). Chronic neuroleptic treatment significantly enhanced the [3H]spiperone Bmax value. EEDQ (6.0 mg/kg, i.p.) produced a similar profound decrease of [3H]spiperone binding site density in both saline- and haloperidol-treated rats. However, the receptor degradation rate constant in the haloperidol-treated animals (k = 0.0051 h-1) and the receptor production rate (r = 1.6 fmol/mg prot/h) were lower than in the saline-treated rats (k = 0.0074 h-1; r = 1.8 fmol/mg prot/h). These results are different from what is found in 6-OH-dopamine lesioned rats. D2-receptor recovery after EEDQ administration is enhanced in chronically (4-5 weeks) denervated striatum (Brain Research, 329 (1985) 225-231) while the degradation rate constant is unchanged. Thus, the present results indicate that chronic haloperidol treatment reduces both the degradation and production rates of striatal D2-receptors.
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
chemical_list: D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D006220:Haloperidol