Modulatory effects of PLG and its peptidomimetics on haloperidol-induced catalepsy in rats

Willard J. Costain, Adam T. Buckley, Margaret C. Evans, Ram K. Mishra, Rodney L. Johnson

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

A behavioral model of dopaminergic function in the rat was used to examine the anticataleptic effects of L-prolyl-L-leucyl-glycinamide (PLG) and peptidomimetic analogs of PLG. Administration of 1 mg/kg PLG intraperitoneally significantly attenuated haloperidol (1 mg/kg)-induced catalepsy (as measured by the standard horizontal bar test), whereas doses of 0.1 and 10 mg/kg PLG did not. Eight synthetic PLG peptidomimetics (Cα, α-dialkylated glycyl residues with lactam bridge constraint [1-4] and without [5-8]) were tested in the same manner (at a dose of 1 μg/kg) and categorized according to their activity, i.e. very active (5), moderately active (2, 3, 4, and 6), and inactive (1, 7, and 8). The catalepsy-reversal action of the diethylglycine-substituted peptidomimetic 5 was examined further and found to exhibit a U-shaped dose-response effect with an optimal dose of 1 μg/kg. The similarity between the effects of PLG and the synthetic peptidomimetics suggests a common mechanism of action. Finally, the synthetic peptidomimetics examined here, particularly peptidomimetic 5, were more effective than PLG in attenuating haloperidol-induced catalepsy. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)761-767
Number of pages7
JournalPeptides
Volume20
Issue number6
DOIs
StatePublished - Aug 1999

Bibliographical note

Funding Information:
This work was supported by NIH Grant NS20036–11. W.J.C. is a recipient of a PMAC-MRC predoctoral fellowship.

Keywords

  • Catalepsy
  • Dopamine
  • Haloperidol
  • PLG
  • Parkinson's disease
  • Peptidomimetic
  • Schizophrenia

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