Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Indiana University School of Medicine, Medical Scientist Training Program, Indianapolis, United States
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Program in Medical Neuroscience, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States
Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States; The Linda and Jack Gill Center for Biomolecular Sciences, Department of Psychological and Brain Science, Program in Neuroscience, Indiana University, Bloomington, United States
Corinne E Metzger
Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, United States
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States
Kaitlin C Reeves
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States
Yong Gao
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States
Hunter Hoffman
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States
Simon N Katner
Deparment of Psychiatry, Indiana University School of Medicine, Indianapolis, United States
Andrea R Masters
Clinical Pharmacology Analytical Core-Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, United States
Cameron W Morris
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Department of Biology, Indiana University-Purdue University, Indianapolis, United States
Erin A Newell
Deparment of Psychiatry, Indiana University School of Medicine, Indianapolis, United States
Eric A Engleman
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States
Anthony J Baucum
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Department of Biology, Indiana University-Purdue University, Indianapolis, United States; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States
Jiuen Kim
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States
Bryan K Yamamoto
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States
Matthew R Allen
Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, United States; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, United States
Yu-Chien Wu
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, United States
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States
Patrick L Sheets
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, United States; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States
Despite the rising prevalence of methadone treatment in pregnant women with opioid use disorder, the effects of methadone on neurobehavioral development remain unclear. We developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. We investigated the effects of PME on physical development, sensorimotor behavior, and motor neuron properties using a multidisciplinary approach of physical, biochemical, and behavioral assessments along with brain slice electrophysiology and in vivo magnetic resonance imaging. Methadone accumulated in the placenta and fetal brain, but methadone levels in offspring dropped rapidly at birth which was associated with symptoms and behaviors consistent with neonatal opioid withdrawal. PME produced substantial impairments in offspring physical growth, activity in an open field, and sensorimotor milestone acquisition. Furthermore, these behavioral alterations were associated with reduced neuronal density in the motor cortex and a disruption in motor neuron intrinsic properties and local circuit connectivity. The present study adds to the limited body of work examining PME by providing a comprehensive, translationally relevant characterization of how PME disrupts offspring physical and neurobehavioral development.