Pharmacological and neurochemical differences between acute and tardive vacuous chewing movements induced by haloperidol |
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Authors: | Michael F Egan Yasmin Hurd Jennifer Ferguson Susan E Bachus Emad H Hamid Thomas M Hyde |
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Institution: | (1) Clinical Research Services, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, 2700 Martin Luther King Jr. Avenue, SE, 20032 Washington, DC, USA;(2) Clinical Brain Disorders Branches, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, 2700 Martin Luther King Jr. Avenue, SE, 20032 Washington, DC, USA;(3) Psychiatry and Psychology Department, Karolinska Hospital, Box 60 500, S-104 01 Stockholm, Sweden |
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Abstract: | Lute 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. |
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Keywords: | Vacuous chewing movements Haloperidol Tardive dyskinesia Substance P Dynorphin Enkephalin |
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