Effects of fentanyl on serotonin syndrome-like behaviors in rats

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• 作者：Sonoe Kitamura ; Takashi Kawano ; Satomi Kaminaga ; Daiki Yamanaka…
• 关键词：Serotonin syndrome ; Fentanyl ; Opioid receptor
• 刊名：Journal of Anesthesia
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：30
• 期：1
• 页码：178-182
• 全文大小：1,399 KB
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• 作者单位：Sonoe Kitamura (1)
  Takashi Kawano (1)
  Satomi Kaminaga (1)
  Daiki Yamanaka (1)
  Hiroki Tateiwa (1)
  Fabricio M. Locatelli (1)
  Masataka Yokoyama (1)
  
  1. Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Anesthesiology
  
• 出版者：Springer Japan
• ISSN：1438-8359

文摘

Emerging evidence from case reports suggests that fentanyl may precipitate potentially life-threatening serotonin syndrome in patients taking serotonergic drugs. However, the underlying mechanism of the association between serotonin syndrome and fentanyl remains under investigation. We therefore investigated the pharmacological effects of an analgesic dose of fentanyl (0.2 mg/kg) injected subcutaneously (s.c.) on serotonergic toxicity-like responses in rats. Rats were s.c. injected with 0.75 mg/kg 8-OH-DPAT, a full 5-HT_1A agonist, as an animal model of serotonin syndrome. The 8-OH-DPAT-treated rats showed well-characterized serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature. Rats injected s.c. with fentanyl alone showed no significant changes in any of the parameters measured, while concomitant administration of fentanyl + 8-OH-DPAT resulted in exaggerated 8-OH-DPAT-induced serototoxic responses. A separate dose–response experiment showed that the serototoxic effect of fentanyl was dose-dependent. Pretreatment with naloxone [2.0 mg/kg, intraperitoneal (i.p.) injection], an opioid receptor antagonist, failed to antagonize the fentanyl-induced exaggerated serotonin syndrome-like behaviors. In contrast, pretreatment with WAY-100653, a serotonin 5-HT_1A receptor antagonist (0.5 mg/kg, i.p. injection) completely inhibited all responses. Our findings provide preclinical proof-of-concept that an analgesic dose of fentanyl enhances serotonin toxicity, likely via its serotonin-reuptake inhibitory activity, independently of interaction with the opioid receptors. Keywords Serotonin syndrome Fentanyl Opioid receptor