| First Author | Baertsch NA | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34402425 | Mgi Jnum | J:355391 |
| Mgi Id | MGI:6741357 | Doi | 10.7554/eLife.67523 |
| Citation | Baertsch NA, et al. (2021) Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network. Elife 10:e67523 |
| abstractText | The analgesic utility of opioid-based drugs is limited by the life-threatening risk of respiratory depression. Opioid-induced respiratory depression (OIRD), mediated by the mu-opioid receptor (MOR), is characterized by a pronounced decrease in the frequency and regularity of the inspiratory rhythm, which originates from the medullary preBtzinger Complex (preBtC). To unravel the cellular- and network-level consequences of MOR activation in the preBtC, MOR- expressing neurons were optogenetically identified and manipulated in transgenic mice in vitro and in vivo. Based on these results, a model of OIRD was developed in silico. We conclude that hyperpolarization of MOR-expressing preBtC neurons alone does not phenocopy OIRD. Instead, the effects of MOR activation are twofold: 1) pre-inspiratory spiking is reduced and 2) excitatory synaptic transmission is suppressed, thereby disrupting network-driven rhythmogenesis. These dual mechanisms of opioid action act synergistically to make the normally robust inspiratory rhythm generating network particularly prone to collapse when challenged with exogenous opioids. |
