Differential effects of acute and chronic administration of haloperidol on substance P and enkephalins in diverse rat brain areas.
Rats received 10 mg/kg/day of haloperidol during up to 9.5 weeks. Substance P, Leu- and Met-enkephalins, were studied in brain using immunohistochemical methods. Haloperidol modified the peptides immunoreactivity in most brain areas. The time necessary to observe the effects of haloperidol on the peptides varied individually, depending on the peptide and the brain area. Moreover, inversions of these effects were often observed, generally occurring between in 5th and 7th day of drug administration. Substance P was increased after haloperidol in the hypophysis, a finding hereto not described. This descriptive study identified none of these three peptides as a single and specific target for dopaminergic receptor blockade. Methodological issues in evaluating the effects of neuroleptics on brain peptides are discussed.
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004743:Enkephalin, Leucine / Q000032:analysis; D004744:Enkephalin, Methionine / Q000032:analysis; D004745:Enkephalins / Q000032:analysis*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000032:analysis*; D013378:Substantia Nigra / Q000187:drug effects; D013997:Time Factors
D004745:Enkephalins; D013373:Substance P; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D006220:Haloperidol