Pharmacological and neurochemical differences between acute and tardive vacuous chewing movements induced by haloperidol

Michael F. Egan, Yasmin Hurd, Jennifer Ferguson, Susan E. Bachus, Emad H. Hamid, Thomas M. Hyde

Research output: Contribution to journalArticle

Abstract

Late onset vacuous chewing movements (VCMs) from chronic neuroleptic treatment have been used as a rat model of tardive dyskinesia (TD). Early onset VCMs have also been observed, raising questions about the validity of this model. To assess the relationship between these two types of VCMs, pharmacological and neurochemical properties of early and late onset VCMs were compared. 'Acute' VCMs were induced by daily intraperitoneal injections for 1-21 days. 'Tardive' VCMs were induced by intramuscular injections of haloperidol decanoate every 3 weeks for 30 weeks followed by a 24-week withdrawal period. Suppression was attempted for both types of VCMs using several doses of intraperitoneal haloperidol. Striatonigral activation was assessed by measuring mRNA expression levels of the neuropeptides dynorphin and substance P using in situ hybridization histochemistry. Enkephalin mRNA was also measured as;an index of striatopallidal activation. The results indicate that acute VCMs cannot be suppressed with increased doses of haloperidol and are associated with reduced dynorphin and substance P. This profile is similar to that seen with an animal model of parkinsonism. Tardive VCMs, in contrast, were markedly suppressed by haloperidol. They have previously been shown to be associated with increased striatonigral activation as indicated by increased dynorphin mRNA. Enkephalin mRNA was elevated following both short and long term treatment. Although superficially similar, acute and tardive VCMs appear to have different pharmacological and neurochemical profiles, suggesting they are related to acute extrapyramidal side effects and tardive dyskinesia, respectively.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalPsychopharmacology
Volume127
Issue number4
DOIs
StatePublished - Nov 5 1996
Externally publishedYes

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Keywords

  • Dynorphin
  • Enkephalin
  • Haloperidol
  • Substance P
  • Tardive dyskinesia
  • Vacuous chewing movements

ASJC Scopus subject areas

  • Pharmacology

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