利鲁唑对吗啡镇痛、耐受和依赖作用的影响(英文)

Effect of riluzole on analgesia,tolerance and dependence of morphine in mice

目的 研究利鲁唑对阿片镇痛、耐受及躯体功能的调节。方法 采用冰醋酸扭体 ,5 5℃热板法和热辐射甩尾法观察利鲁唑对小鼠痛阈及吗啡镇痛效应的影响 ;采用小鼠急性和慢性吗啡耐受模型及小鼠吗啡依赖模型 ,观察利鲁唑对吗啡耐受和依赖的作用。结果 单独皮下注射利鲁唑 2 .5～ 10mg·kg- 1在以上 3种模型无镇痛作用 ,然而能剂量依赖性地增强吗啡镇痛效应。利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地对抗吗啡引起的急性和慢性耐受。在小鼠吗啡依赖模型中 ,利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地抑制吗啡戒断症状的产生。结论 利鲁唑自身无镇痛作用 ,但能显著增强吗啡镇痛效应 。

AIM To investigate the effects of riluzole(2 amino 6 trifluoromethoxy benzothiazole) on opioid actions in mice. METHODS The effects of riluzole on pain threshold and morphine analgesia were observed in acetic acid writhing test, 55℃ hot plate test and heat radiation tail flick assay. The effects of riluzole on acute and chronic morphine tolerance and physical dependence in mice were observed. RESULTS In mouse acetic acid writhing test, 55℃ hot plate test and heat radiation tail flick assay, riluzole(2.5 to 10 mg·kg -1 , sc) administrated 20 min before morphine administration enhanced morphine analgesia in a dose dependent manner. However, riluzole(10 mg·kg -1 ) alone had no analgesic effects. Riluzole(2.5 to 10 mg·kg -1 ) prevented the development of tolerance to morphine in a dose dependent manner in acute and chronic tolerance models. In substance dependence experiment, withdrawal jumps and loss in body weight precipitated by naloxone in morphine dependent mice were inhibited by co administration of riluzole(2.5 to 10 mg·kg -1 , sc) with morphine in a dose dependent manner. CONCLUSION Riluzole is not able to elevate the pain threshold, but enhances morphine analgesia, inhibits tolerance to and dependence on morphine in mice.