한성 (The Salk Institute for Biological Studies, University of California San Diego) | 한빛사논문 > 한빛사

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The Salk Institute for Biological Studies, University of California San Diego

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Proc. Natl. Acad. Sci. USA, June 8, 2021, 118 (23) : e2022134118 | https://doi.org/10.1073/pnas.2022134118 Neural basis of opioid-induced respiratory depression and its rescue

Shijia Liu^a,b, Dong-Il Kim^a, Tae Gyu Oh^c, Gerald M. Pao^d, Jong-Hyun Kim^a, Richard D. Palmiter^e,f, Matthew R. Banghart^b, Kuo-Fen Lee^a,b, Ronald M. Evans^c,g, and Sung Han^a,b,1

^aPeptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA 92037; ^bSection of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093; ^cGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; ^dMolecular and Cellular Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA 92037; ^eHHMI, University of Washington, Seattle, WA 98195; ^fDepartment of Biochemistry, School of Medicine, University of Washington, Seattle, WA 98195; and ^gHHMI, The Salk Institute for Biological Studies, La Jolla, CA 92037

¹To whom correspondence may be addressed.

Abstract

Opioid-induced respiratory depression (OIRD) causes death following an opioid overdose, yet the neurobiological mechanisms of this process are not well understood. Here, we show that neurons within the lateral parabrachial nucleus that express the µ-opioid receptor (PBLOprm1 neurons) are involved in OIRD pathogenesis. PBLOprm1 neuronal activity is tightly correlated with respiratory rate, and this correlation is abolished following morphine injection. Chemogenetic inactivation of PBLOprm1 neurons mimics OIRD in mice, whereas their chemogenetic activation following morphine injection rescues respiratory rhythms to baseline levels. We identified several excitatory G protein–coupled receptors expressed by PBLOprm1 neurons and show that agonists for these receptors restore breathing rates in mice experiencing OIRD. Thus, PBLOprm1 neurons are critical for OIRD pathogenesis, providing a promising therapeutic target for treating OIRD in patients.

parabrachial nucleus, μ-opioid receptor, OIRD

논문정보

형식Research article
게재일2021년 06월 (BRIC 등록일 2021-06-11)
연구진국외 연구진
분야 생명과학 > 신경생물학

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