Mechanisms of opioid drug action in the respiratory rhythm-generating preBötzinger complex

Opioid drugs bind receptors in the brainstem preBötzinger complex (preBötC) to slow the breathing rhythm, but the underlying mechanisms of opioid drug action in the site are poorly understood. Here, we investigate mechanisms in brainstem slices from mice that capture the preBötC and remain rhythmically active in vitro using imaging and electrophysiological approaches. We show that the number of rhythmically active preBötC neurons is not reduced by opioid drugs. We also show that opioid drugs inhibit synaptic release in excitatory terminals within the site. A clearer understanding of how opioid drugs act within the brainstem to depress breathing may guide the development of more effective treatments for opioid-induced respiratory depression.