Acute and late onset movement disorders frequently complicate the treatment of 
psychosis with typical neuroleptic drugs like haloperidol, but not with atypical 
neuroleptic drugs like clozapine. Although the neural mechanisms underlying 
neuroleptic-induced movement disorders remain unknown, alterations in basal 
ganglia function are likely involved. A potential role for the endogenous opiate 
peptides in neuroleptic-induced movement disorders is suggested by the 
immunocytochemical localization of met5-enkephalin (ME) in the striatopallidal 
projection pathway, and by the increased levels of ME measured by 
radioimmunoassay in the rat caudate-putamen nuclei (CPN) following haloperidol 
treatment. We sought to determine whether met5-enkephalin-like immunoreactivity 
(MELI) in terminal fields within globus pallidus and in perikarya in CPN was 
differentially altered in rats chronically treated with haloperidol or 
clozapine. Acrolein-fixed forebrain sections were collected from cohorts of 
adult rats receiving 21-day oral administration of haloperidol, clozapine, or 
water. Sections from the three treatment groups were collectively processed for 
immunocytochemical labeling using varying dilutions of ME antiserum and the 
avidin-biotin peroxidase method. In globus pallidus, densitometry measures 
revealed significantly increased levels of immunoperoxidase labeling for ME in 
haloperidol-treated, but not in clozapine-treated animals. In CPN, optical 
densitometry as well as cell counting measurements also showed a significant 
increase in MELI only in the haloperidol-treated group. These results support 
the concept that alterations in endogenous opiate peptides in basal ganglia may 
contribute to movement disorders seen in patients receiving typical neuroleptic 
drugs.(ABSTRACT TRUNCATED AT 250 WORDS)