Why the study?
Opioid-induced respiratory depression causes death following opioid overdose, but the underlying neurobiological mechanisms are not well understood.
Does activation of PBL Oprm1 neurons rescue opioid-induced respiratory depression in mouse models?
Does activation of PBL Oprm1 neurons rescue opioid-induced respiratory depression in mouse models?
Activation of mu-opioid receptor-expressing neurons in the lateral parabrachial nucleus can rescue opioid-induced respiratory depression in mice, identifying a potential therapeutic target.
Suggests novel neural targets for OIRD prevention; leaves open clinical translation and therapeutic development.
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.
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Liu et al. (2020) studied this question.
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