Prescription opioid overdose is increasing at a rapid rate. Respiratory depression is the primary cause of death from opioid overdose, yet surprisingly, very little is known about the mechanisms of opioid-induced respiratory depression. Breathing, like other motor behaviors, is coordinated by a central neural network. The goal of our laboratory is to understand how opioids modulate neurons in the respiratory network to cause breathing disturbances. A variety of cellular and systems level approaches—including brain slice electrophysiology, single unit and whole nerve recordings from a unique preparation with an intact respiratory network and in vivo-like respiratory cycle, and plethysmography in awake animals—are used to achieve this goal.
- Levitt ES, Williams JT. Desensitization and Tolerance of Mu Opioid Receptors on Pontine Kölliker-Fuse Neurons. Mol Pharmacol. 2018 Jan;93(1):8-13. doi: 10.1124/mol.117.109603. Epub 2017 Nov 2.
- Gantz SC, Levitt ES, Llamosas N, Neve KA, Williams JT. Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA. Cell Rep. 2015 Aug 11;12(6):944-54. doi: 10.1016/j.celrep.2015.07.005. Epub 2015 Jul 30.
- Levitt ES, Abdala AP, Paton JF, Bissonnette JM, Williams JT. μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive. J Physiol. 2015 Oct 1;593(19):4453-69. doi: 10.1113/JP270822. Epub 2015 Aug 19.
- Levitt ES, Hunnicutt BJ, Knopp SJ, Williams JT, Bissonnette JM. A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett syndrome. J Appl Physiol (1985). 2013 Dec;115(11):1626-33. doi: 10.1152/japplphysiol.00889.2013. Epub 2013 Oct 3.