L-Prolyl-L-leucyl-glycinamide and its peptidomimetic analog 3(R)-[(2(S)-pyrrolidylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) attenuate haloperidol-induced c-fos expression in the striatum

Michael C. Ott, Willard J. Costain, Ram K. Mishra, Rodney L. Johnson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Acute treatment of rats with haloperidol results in a rapid and transient increase in striatal c-fos mRNA and Fos immunoreactivity. The induction of immediate early genes by haloperidol may be involved in the development of extrapyramidal side effects. L-Prolyl-L-leucyl-glycinamide (PLG, or MIF-1) has been observed to antagonize the development of haloperidol-induced D2 receptor supersensitivity in rats. We investigated the modulatory effects of PLG on haloperidol-induced c-fos and Fos protein expression in the rat striatum. We report that coadministration of either PLG or the potent analog of PLG, 3(R)-[(2(S)-pyrrolidylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), attenuated haloperidol-induced c-fos and Fos expression. Haloperidol induced [2 mg/kg, intraperitoneally (i.p.)] c-fos and Fos expression by 500% and 100%, respectively. These responses were attenuated by 170% and 75%, respectively, when coadministered with PLG (20 mg/kg, i.p.) or by 79% by PAOPA (10 μg/kg, i.p.). Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalPeptides
Volume21
Issue number2
DOIs
StatePublished - Feb 2000

Keywords

  • Dopamine
  • Immediate-early genes
  • Neuroleptics
  • PLG
  • Striatum
  • c-fos

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