Differential alterations in striatal dopamine receptor sensitivity induced by repeated administration of clinically equivalent doses of haloperidol, sulpiride or clozapine in rats.
Rats received therapeutically equivalent doses of either haloperidol (1.7-1.9 mg/kg/day), sulpiride (112-116 mg/kg/day) or clozapine 30-35 mg/kg/day) continuously for 4 weeks. Treatment with haloperidol, but not sulpiride or clozapine, caused inhibition of stereotyped behaviour induced by apomorphine (0.125-0.25 mg/kg SC). Following drug withdrawal for up to 7 days, haloperidol and sulpiride, but not clozapine treatment caused an exaggeration of stereotyped behaviour induced by apomorphine. Bmax values for striatal 3H-spiperone binding were elevated in animals treated for 2 and 4 weeks with haloperidol, but not with sulpiride or clozapine. Following drug withdrawal, haloperidol, but not sulpiride or clozapine, treatment caused an increase in Bmax for striatal 3H-spiperone binding. Bmax values for striatal 3H-NPA binding revealed no change during haloperidol or clozapine treatment. Sulpiride treatment for 1 week caused an increase in Bmax for 3H-NPA binding, which returned to control levels at 2 and 4 weeks. Following drug withdrawal, there was an increase in Bmax for 3H-NPA binding in rats treated with haloperidol and sulpiride, but not clozapine. On continuous treatment and following withdrawal from haloperidol, sulpiride, or clozapine the ability of dopamine to stimulate striatal adenylate cyclase activity did not differ from that in control animals. Repeated administration of sulpiride or clozapine may not induce striatal dopamine receptor supersensitivity when given in clinically relevant doses, although haloperidol does.
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003984:Dibenzazepines / Q000494:pharmacology*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology*
D003984:Dibenzazepines; D011954:Receptors, Dopamine; D013134:Spiperone; C009074:N-n-propylnorapomorphine; D013469:Sulpiride; D003024:Clozapine; D006220:Haloperidol; D001058:Apomorphine