TY - JOUR
T1 - Dopamine, acetylcholine, and GABA effects in acute dystonia in primates
AU - Casey, Daniel E.
AU - Gerlach, Jes
AU - Christensson, Erik
PY - 1980/9
Y1 - 1980/9
N2 - 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.
AB - 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.
KW - Acetylcholine
KW - Dopamine
KW - Extrapyramidal symptoms
KW - GABA Dystonia
KW - Neuroleptics
KW - Primates
UR - http://www.scopus.com/inward/record.url?scp=0018875644&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018875644&partnerID=8YFLogxK
U2 - 10.1007/BF00432375
DO - 10.1007/BF00432375
M3 - Article
C2 - 6775341
AN - SCOPUS:0018875644
SN - 0033-3158
VL - 70
SP - 83
EP - 87
JO - Psychopharmacology
JF - Psychopharmacology
IS - 1
ER -