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 5 μmol/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 4.21 μmol/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.

Aim: To examine the effects of fentanyl, a potent mu-opioid receptor (MOR) agonist, on-air puff-evoked responses in Purkinje cells (PCs), and molecular layer interneurons (MLIs) using in vivo patch-clamp recordings in anesthetized mice. Methods: Male mice 6-8 weeks-old were anesthetized and fixed on a custom-made stereotaxic frame. The cerebellar surface was exposed and perfused with oxygenated artificial cerebrospinal fluid (ACSF). Patch-clamp recordings in the cell-attached mode were obtained from PCs and MLIs. Facial stimulation by air-puff of the ipsilateral whisker pad was performed through a pressurized injection system. Fentanyl citrate, CTOP, and H-89 dissolved in ACSF were perfused onto the cerebellar surface. Results: Fentanyl significantly inhibited the amplitude and area under the curve (AUC) of sensory stimulation-evoked inhibitory responses in PCs. Although fentanyl did not influence the frequency of simple spikes (SSs), it decreased the pause of SS. The IC50 of the fentanyl-induced suppression of the P1 response amplitude was 5.53 μM. The selective MOR antagonist CTOP abolished fentanyl-induced inhibitory responses in PCs. However, the application of CTOP alone increased the amplitude, AUC of P1, and the pause of SS. Notably, fentanyl significantly inhibited the tactile-evoked response of MLIs but did not affect their spontaneous firing. The fentanyl-induced decrease of inhibitory responses in PCs was partially prevented by a PKA inhibitor, H-89. Conclusions: These results suggest that fentanyl binds to MORs in MLIs to reduce GABAergic neurotransmission in MLI-PC projections and one potential mechanism is via modulation of the cAMP-PKA pathway.

Objective To observe the level changes of glutamate(Glu) and aspartic acid (ASP) in the Rostral Ventrolateral Medulla(RVLM) in sodium nitroprusside (SNP)-induced acute hypotension.Methods Forty adult male Wistar rats were divided into four groups:sham-operated group(Sham),bilateral labyrinthectomy group(BL),sinoaortic denervation group(SAD) and SAD+BL group.To investigate the level changes of Glu and ASP in RVLM in Sham,BL,SAD,SAD+BL groups following SNP infusion.Results (1)Infusion SNP decreased the mean blood pressure in Sham,BL,SAD and BL+SAD groups,and the blood pressure return to the baseline when infusion finished.(2) There was no significant difference in the level of Glu and ASP release in the RVLM in 4 groups before SNP infusion.(3) The level of Glu and ASP release peaked 10 min after SNP infusion in all 4 groups,and the level of Glu and ASP in BL,SAD and BL+ SAD groups were obviously decreased compared with Sham group.