Neuroleptic-induced striatal dopamine receptor supersensitivity in mice: relationship to dose and drug.
Clozapine and molindone administered to mice for 21 days did not elevate the density of striatal 3H-spiperone binding sites at doses clinically equivalent to 1.5 mg/kg haloperidol, which elevated binding by 29%. Thioridazine (25 mg/kg) elevated binding by 25%. It appears that clinically equivalent doses of clozapine and molindone have reduced ability to induce striatal D-2 dopamine receptor supersensitivity. These data are discussed in relationship to in vitro potencies and toxicity. The dose-response relationship of chronic haloperidol treatment and specific striatal 3H-spiperone binding was complex, i.e., binding was elevated at all doses, but the dose-response curve was concave upward. These data suggest that supersensitization is a complex interactive phenomenon comprised of elevation of striatal D-2 dopamine receptor density and other compensatory mechanisms.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D013134:Spiperone; D006220:Haloperidol