Quantitative light microscopic demonstration of increased pallidal and striatal met5-enkephalin-like immunoreactivity in rats following chronic treatment with haloperidol but not with clozapine: implications for the pathogenesis of neuroleptic-induced movement disorders.
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)
Auchus
A P
AP
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021.
Pickel
V M
VM
D000818:Animals; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004744:Enkephalin, Methionine / Q000032:analysis / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D008959:Models, Neurological; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D014867:Water
D014867:Water; D004744:Enkephalin, Methionine; D003024:Clozapine; D006220:Haloperidol