Dopamine, acetylcholine, and GABA effects in acute dystonia in primates

Daniel E. Casey, Jes Gerlach, Erik Christensson

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Neurological side effects associated with neuroleptic drugs result from a complex interaction of multiple neurotransmitters. To clarify the etiology of neuroleptic-induced acute dystonic reactions, monkeys (Cercopithecus aethiops) were treated with haloperidol at doses sufficient to evoke dystonia, and the effects of agents that influenced dopaminergic, cholinergic, or GABAergic neurotransmitters were evaluated. Apomorphine, a dopamine (DA) agonist, and biperiden, an acetylcholine (ACh) antagonist, decreased acute dystonia, whereas α-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis, and physostigmine, and ACh agonist, increased the symptoms. Muscimol, a GABA agonist, increased the dystonias in a dose-dependent way, and GABA inhibition with picrotoxin also aggravated dystonia, complicated by systemic intoxication and seizures. The reciprocal interaction between DA and ACh influences is consistent with clinical findings and animal models of dyskinesias. Dystonia may also be modulated by GABAergic substrates, but the results suggest complex interactions among DA, ACh, and GABA neurotransmission. Symptoms involving the orofacial, limb, and trunk regions, and purposeless overactivity are discussed in comparison with acute and tardive neuroleptic-induced movement disorders.

Original languageEnglish (US)
Pages (from-to)83-87
Number of pages5
JournalPsychopharmacology
Volume70
Issue number1
DOIs
StatePublished - Sep 1 1980

Keywords

  • Acetylcholine
  • Dopamine
  • Extrapyramidal symptoms
  • GABA Dystonia
  • Neuroleptics
  • Primates

ASJC Scopus subject areas

  • Pharmacology

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