Year: 2021
Type: article
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 (PBL Oprm1 neurons) are involved in OIRD pathogenesis. PBL Oprm1 neuronal activity is tightly correlated with respiratory rate, and this correlation is abolished following morphine injection. Chemogenetic inactivation of PBL Oprm1 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 PBL Oprm1 neurons and show that agonists for these receptors restore breathing rates in mice experiencing OIRD. Thus, PBL Oprm1 neurons are critical for OIRD pathogenesis, providing a promising therapeutic target for treating OIRD in patients.
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: High-throughput mapping of selectively vulnerable cell types and projections in aging and Alzheimer's Disease, Modeling Alzheimer's Disease Related Dementias in the Marmoset, Contribution of the Parabrachial CGRP-Expressing Neurons to the Pathophysiology of Panic Disorder, Glycosylation of the perineuronal net in Alzheimer's Disease, Center for Epigenomics of the Mouse Brain Atlas (CEMBA), G5543838326, G6900861361, Development of marmoset models of neurodegenerative disease using embryonic stem cell-based gene-editing approaches, G7213700913, Modeling Alzheimer's Disease Related Dementias in the Marmoset, Genetic models of sporadic Alzheimers Disease in the marmoset, Compartment-specific signaling of striatal opioid peptides in reward-guided behavior, G921629941
OpenAlex ID: W3165288569