Effects of haloperidol on cholinergic striatal interneurons: relationship to oral dyskinesias

J Neural Transm (Vienna). 2004 Aug;111(8):1075-91. doi: 10.1007/s00702-004-0131-1. Epub 2004 Apr 2.


In a subset of rats, typical antipsychotic drugs (tAPD) produce oral dyskinesias called vacuous chewing movements (VCMs) that resemble tardive dyskinesia (TD), a behavioral side effect seen in a subset of people following tAPD treatment. Morphological changes within the striatum following tAPD have been correlated to VCMs in animal models. The cholinergic system has been implicated in expression of TD. To test the hypothesis that the striatal cholinergic system is perturbed after haloperidol treatment, rats were administered haloperidol for three weeks and tested for VCMs; the striata were then processed for the immunocytochemical localization of choline-acetyltransferase (ChAT). Neuronal density measures of ChAT-labeled neurons showed a 22% decrease in haloperidol-treated versus controls rats and a 37% reduction in the lateral portion of the striatum only in rats with VCMs. These findings further support evidence of the possible involvement of the cholinergic system and the ventrolateral striatum in VCMs, and possibly TD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Cell Count
  • Choline O-Acetyltransferase / metabolism
  • Dyskinesia, Drug-Induced / enzymology
  • Dyskinesia, Drug-Induced / physiopathology*
  • Haloperidol / pharmacology*
  • Interneurons / drug effects*
  • Interneurons / enzymology
  • Neostriatum / cytology
  • Neostriatum / drug effects*
  • Neostriatum / enzymology
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / enzymology
  • Parasympathetic Nervous System / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Antipsychotic Agents
  • Choline O-Acetyltransferase
  • Haloperidol