Pro-Leu-glycinamide and its peptidomimetic, PAOPA, attenuate haloperidol induced vacuous chewing movements in rat: A model of human tardive dyskinesia

S. Sharma, P. Paladino, J. Gabriele, H. Saeedi, P. Henry, M. Chang, R. K. Mishra, R. L. Johnson

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

In the present experimental paradigm, we examine the effect of L-prolyl-L-leucyl-glycinamide (PLG) co-administration with haloperidol on vacuous chewing movements (VCM) in rats - a model of tardive dyskinesia (TD) in humans. We examined the dose dependent induction of VCM through both injected and orally administered PLG (MIF-1). Our results show significant levels of VCM attenuation (P<0.05) in rats treated with 10mg/kg of PLG. Doses of 1 and 100mg/kg were ineffective. Reductions were present in both orally treated and injected rats. We also examined the therapeutic effect of a peptidomimetic of PLG - PAOPA. PAOPA was able to produce similar behavioral effects to PLG at a dose, which was 100-fold lower than the effective dose of PLG. These results suggest that PLG may play a role in D2 receptor expression and function, as well as providing a therapy for neuroleptic induced TD.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalPeptides
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2003

Bibliographical note

Funding Information:
This work was supported by NIH 20036 (USA) and NESRC (Canada).

Keywords

  • (MIF-1)
  • Haloperidol
  • PAOPA
  • PLG
  • Tardive dyskinesia
  • VCM

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