AUTHOR=Yang He-Min , Zhan Li-Jie , Lin Xue-Qin , Chu Chun-Ping , Qiu De-Lai , Lan Yan 

TITLE=Fentanyl Inhibits Air Puff-Evoked Sensory Information Processing in Mouse Cerebellar Neurons Recorded in vivo

JOURNAL=Frontiers in Systems Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/systems-neuroscience/articles/10.3389/fnsys.2020.00051

DOI=10.3389/fnsys.2020.00051

ISSN=1662-5137

ABSTRACT=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 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. 
Resluts: 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 (SS), it decreased the pause of SS. The IC50 of the fentanyl-induced suppression of P1 response amplitude was 5.53 μM. The selective MOR antagonist CTOP abolished fentanyl-induced inhibitory responses in PCs. However, 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.