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Role of cortical and striatal 5-HT1A receptors in alleviating antipsychotic-induced extrapyramidal disorders.

Abstract
Previous studies have revealed that 5-HT(1A) agonists ameliorate antipsychotic-induced extrapyramidal symptoms (EPS) through postsynaptic 5-HT(1A) receptors. Here, we conducted an intracerebral microinjection study of (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin ((+/-)8-OH-DPAT) to determine the action site of the 5-HT(1A) agonist in alleviating EPS. Bilateral microinjection of(+/-)8-OH-DPAT (5 microg/1microL per side) either into the primary motor cortex (MC) or the dorsolateral striatum (dlST) significantly attenuated haloperidol-induced catalepsy in rats. The anticataleptic action of (+/-)8-OH-DPAT was more prominent with the MC injection than with the dlST injection. WAY-100135 (a selective 5-HT(1A) antagonist) completely antagonized the reversal of haloperidol-induced catalepsy both by intracortical and intrastriatal (+/-)8-OH-DPAT. Furthermore, lesioning of dopamine neurons with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg/day, i.p., for 4 days) did not alter the anti-EPS actions of (+/-)8-OH-DPAT in a mouse pole test. The present results strongly suggest that 5-HT(1A) agonist alleviates antipsychotic-induced EPS by activating postsynaptic 5-HT(1A) receptors in the MC and dlST, probably through non-dopaminergic mechanisms.
AuthorsSaki Shimizu, Ayaka Tatara, Junta Imaki, Yukihiro Ohno
JournalProgress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 34 Issue 6 Pg. 877-81 (Aug 16 2010) ISSN: 1878-4216 [Electronic] England
PMID20398719 (Publication Type: Journal Article)
CopyrightCopyright (c) 2010 Elsevier Inc. All rights reserved.
Chemical References
  • Antipsychotic Agents
  • Hydroxydopamines
  • Piperazines
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • WAY 100135
  • Haloperidol
Topics
  • Animals
  • Antipsychotic Agents (pharmacology)
  • Basal Ganglia Diseases (chemically induced, metabolism)
  • Corpus Striatum (drug effects, metabolism)
  • Haloperidol (pharmacology)
  • Hydroxydopamines (pharmacology)
  • Male
  • Microinjections
  • Motor Cortex (drug effects, metabolism)
  • Neurons (drug effects, metabolism)
  • Piperazines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A (metabolism)
  • Serotonin Antagonists (pharmacology)
  • Statistics, Nonparametric

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