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.