Dopamine receptor subtypes: differential regulation after 8 months treatment with antipsychotic drugs.
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.
Florijn
W J
WJ
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey, USA.
Tarazi
F I
FI
Creese
I
I
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000378:metabolism; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D009928:Organ Specificity; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000096:biosynthesis* / Q000145:classification; D011985:Receptors, Serotonin / Q000096:biosynthesis; D012457:Salicylamides / Q000378:metabolism / Q000494:pharmacology*; D013134:Spiperone / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D015854:Up-Regulation / Q000187:drug effects*
D014150:Antipsychotic Agents; D001549:Benzamides; D001552:Benzazepines; D007457:Iodine Radioisotopes; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D014316:Tritium; D020891:Raclopride; D013134:Spiperone; D003024:Clozapine; D006220:Haloperidol; C030265:nemonapride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin