Concurrent treatment with benztropine and haloperidol attenuates development of behavioral hypersensitivity but not dopamine receptor proliferation.

Groups of male rats (n = 16 each) were treated with normal saline, haloperidol (0.75 mg/kg), benztropine (1.8 mg/kg) or haloperidol and benztropine once a day for 24 days. Following a 96 hour drug free interval, subsets of these animals were assessed for apomorphine-induced (0.75 mg/kg) stereotypic behavior, sacrificed and analyzed for striatal dopamine biochemistry or sacrificed and analyzed for spiroperidol binding sites. Benztropine cotreatment attenuated the development of behavioral hypersensitivity to haloperidol but did not alter either the dopamine receptor proliferation or the striatal dopamine biochemical changes induced by haloperidol. These results suggest that behavioral hypersensitivity is not an automatic manifestation of dopamine receptor proliferation but must depend, in part, on other factors.