Chronic neuroleptic treatment does not suppress the dynamic characteristics of the dopaminergic receptor D2 system

1. Rats were treated with either haloperidol (0.5 mg/kg) or haloperidol plus an anticholinergic drug (0.5 and 0.15 mg/kg/day respectively) for 3 days, 7 days and 16 months. 2. Estimates made twenty hours after the last doses showed that haloperidol reduced the concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and the olfactory tubercle. 3. A challenge dose of either haloperidol or haloperidol plus an anticholinergic drug was administered to rats pretreated with haloperidol or haloperidol plus an anticholinergic drug; this challenge dose reversed the reduction in dopamine metabolites caused by neuroleptic administration. 4. After sixteen months of haloperidol administration dopamine levels were reduced, but adding an anticholinergic drug to haloperidol treatment prevented this reduction in dopamine concentration.