芬太尼经中间神经元减弱吹风刺激诱发的小鼠小脑分子层场电位反应

芬太尼作为一种合成的阿片类药物,可与μ型阿片受体(mu-opioid receptor,MOR)结合产生镇痛、镇静及奖赏相关的行为。小脑的功能不仅局限于对躯体平衡、肌张力和随意运动的调节,还有情绪调节、认知和学习记忆等功能。有研究表明,小脑中广泛分布着功能性的MOR,但其对小脑功能的影响还未见报道。本文旨在采用在体电生理学方法研究枸橼酸芬太尼对同侧触须垫吹风刺激诱发的小鼠小脑分子层场电位反应的影响。结果显示,小脑表面灌流5μmol/L芬太尼可使吹风刺激诱发的小脑分子层场电位反应中正向波(P1)的振幅、半宽和曲线下面积显著降低,对P1振幅的半数有效抑制浓度为4.21μmol/L。芬太尼的这种抑制效应可被MOR特异性阻断剂CTOP所阻断。单独给予CTOP则增加P1的振幅和曲线下面积。芬太尼还可显著抑制分子层中间神经元(molecular layer interneurons,MLIs)自发和诱发的放电数目。以上结果表明,芬太尼可减弱吹风刺激诱发的分子层场电位反应,其机制可能与芬太尼通过作用于MOR抑制MLIs的自发和诱发放电活动有关。

Fentanyl attenuates air-puff stimulus-evoked field potential response in the cerebellar molecular layer via inhibiting interneuron activity in mice

Fentanyl as a synthetic opioid works by binding to the mu-opioid receptor(MOR)in brain areas to generate analgesia,sedation and reward related behaviors.As we know,cerebellum is not only involved in sensory perception,motor coordination,motor learning and precise control of autonomous movement,but also important for the mood regulation,cognition,learning and memory.Previous studies have shown that functional MORs are widely distributed in the cerebellum,and the role of MOR activation in cerebellum has not been reported.The aim of the present study was to investigate the effects of fentanyl on air-puff stimulus-evoked field potential response in the cerebellar molecular layer using in vivo electrophysiology in mice.The results showed that perfusion of 5μmol/L fentanyl on the cerebellar surface significantly inhibited the amplitude,half width and area under the curve(AUC)of sensory stimulation-evoked inhibitory response P1 in the molecular layer.The half-inhibitory concentration(IC50)of the fentanyl-induced suppression of P1 amplitude was 4.21μmol/L.The selective MOR antagonist CTOP abolished fentanyl-induced inhibitory responses in the molecular layer.However,application of CTOP alone increased the amplitude and AUC of P1.Notably,fentanyl significantly inhibited the tactile stimulation-evoked response of molecular layer interneurons(MLIs)and the spontaneous firing of MLIs.The results suggest that fentanyl attenuates air-puff stimulus-evoked field potential response in the cerebellar molecular layer via binding to MOR to restrain the spontaneous and evoked firing of MLIs.