Exploring Endogenous Opioid Influence on Respiratory Development

After nine months in the aqueous uterine environment, a newborn’s first breath of air is a major transition for the respiratory system. Initially, breathing is slow with periodic apneas. Many factors contribute to slow breathing at birth, including immature ventilatory reflexes and developing neuromodulatory systems. Administration of the non-selective opioid receptor antagonist naloxone increases breathing rate in neonatal mammals. Therefore, I hypothesized that endogenous opioid peptides suppress breathing during birth and contribute to unstable breathing during early life. To test this hypothesis, I measured breathing in mice lacking mu-opioid receptors (MOR-KO) and wild type littermate control mice at multiple developmental time points. Breathing was measured using a small piezoelectric sensor placed beneath the chest cavity. Body temperature was carefully monitored and maintained using a heating pad. Both MOR-KO and wild type mice followed similar developmental trajectories; breathing faster and more regularly as they aged. At postnatal day 0 (P0), MOR-KO mice breathed faster than wild type mice of the same age. However, this difference diminished as mice aged, and breathing rate was not different at P4 or older time points. Breathing was the most variable on P0 for both MOR-KO and wild type mice, suggesting that breathing variability is independent of mu opioid receptors. Results suggest that endogenous opioids suppress respiratory rate by activating mu opioid receptors on P0. But, many questions remain about the mechanisms of endogenous opioids and breathing development including the type of endogenous opioid peptide and location of mu opioid receptors responsible for this effect. Future work will measure breathing in mice lacking the endogenous opioid precursor peptide proenkephalin and mice with pons-targeted and medulla-targeted deletion of mu opioid receptors. Understanding the fundamental role of the endogenous opioid system in respiratory development is important since modulating the endogenous opioid system could be an effective way to improve breathing rate during early life, especially in premature infants who are prone to oxygen desaturating events. This research is funded by the T32 Multidisciplinary Postdoctoral Training Program in Biology of Drug Abuse to JWF. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.