論文

査読有り
2013年10月

5-HT1A agonist alleviates serotonergic potentiation of extrapyramidal disorders via postsynaptic mechanisms

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
  • Saki Shimizu
  • ,
  • Yuto Mizuguchi
  • ,
  • Ayaka Tatara
  • ,
  • Tomoya Kizu
  • ,
  • Saki Andatsu
  • ,
  • Akira Sobue
  • ,
  • Mai Fujiwara
  • ,
  • Tomoki Morimoto
  • ,
  • Yukihiro Ohno

46
開始ページ
86
終了ページ
91
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.pnpbp.2013.06.016
出版者・発行元
PERGAMON-ELSEVIER SCIENCE LTD

We previously demonstrated that 5-HT stimulants, including selective serotonin reuptake inhibitors (SSRIs), potentiated antipsychotic-induced extrapyramidal symptoms (EPS) by stimulating 5-HT2A/2C, 5-HT3 and 5-HT6 receptors. Here, we studied the effects of the 5-HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin ((+/-)-8-OH-DPAT) on the fluoxetine enhancement of EPS (i.e., bradykinesia and catalepsy) to determine if the 5-HT1A agonist can counteract the serotonergic potentiation of EPS. Fluoxetine did not induce EPS signs by itself, but significantly potentiated haloperidol-induced bradykinesia in mice. (+/-)-8-OH-DPAT (0.1-1 mg/kg, i.p.) significantly attenuated the fluoxetine enhancement of haloperidol-induced bradykinesia in a dose-dependent manner. A selective 5-HT1A antagonist (s)-WAY-100135 completely reversed the anti-EPS action of (+/-)-8-OH-DPAT. Microinjection studies using rats revealed that local application of (+/-)-8-OH-DPAT into the dorsolateral striatum or the motor cortex significantly diminished fluoxetine-enhanced catalepsy. In contrast, (+/-)-8-OH-DPAT injected into the medial raphe nucleus failed to affect EPS induction. The present results illustrate that 5-HT1A agonist can alleviate the SSRI enhancement of EPS by activating postsynaptic 5-HT1A receptors in the striatum and cerebral cortex. (C) 2013 Elsevier Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.pnpbp.2013.06.016
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000324480900014&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.pnpbp.2013.06.016
  • ISSN : 0278-5846
  • eISSN : 1878-4216
  • Web of Science ID : WOS:000324480900014

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