Neural basis of opioid-induced respiratory depression and its rescue

Opioid-induced respiratory depression (OIRD) is the direct cause of death from opioid overdose, which accounts for the current global opioid crisis. Here, we report that neurons expressing the μ-opioid receptors in the lateral parabrachial nucleus of the pontine respiratory group are necessary and sufficient for the pathogenesis of OIRD. Activating these neurons through endogenous or artificial G protein-coupled receptor signaling pathways rescues OIRD in intact mice, suggesting its therapeutic utility in OIRD patients.