Perinatal Fentanyl Exposure Leads to Long-Lasting Impairments in Somatosensory Circuit Function and Behavior

• DOI: 10.1523/jneurosci.2470-20.2020
• Publication Date: 2021-01-19T22:07:28Z
• Authors: Jason B. Alipio; Catherine Haga; Megan E. Fox; Keiko Arakawa; Rakshita Balaji; Nathan Cramer; Mary Kay Lobo; Asaf Keller
• Keywords: Somatosensory evoked potential

One consequence of the opioid epidemic are lasting neurodevelopmental sequelae afflicting adolescents exposed to opioids in womb. A translationally relevant and developmentally accurate preclinical model is needed understand behavioral, circuit, network, molecular abnormalities resulting from this exposure. By employing a novel perinatal fentanyl exposure, our data reveal that has several dose-dependent, developmental consequences somatosensory function behavior. Newborn male female mice exhibit signs withdrawal sensory-related deficits extend at least adolescence. As exposure does not affect dams' health or maternal behavior, these effects result direct actions on pups' developing brain. At adolescence, reduced adaptation sensory stimuli, corresponding impairment primary (S1) function. In vitro electrophysiology demonstrates long-lasting reduction S1 synaptic excitation, evidenced by decreases release probability, NMDA receptor-mediated postsynaptic currents, frequency miniature excitatory as well increased inhibitory currents. contrast, anterior cingulate cortical neurons an opposite phenotype, with excitation. Consistent changes, electrocorticograms suppressed ketamine-evoked γ oscillations. Morphological analysis pyramidal indicate dendritic complexity, length, soma size. Further, exhibited abnormal mRNA expression key receptors neuronal growth development, changes were consistent electrophysiological morphological changes. These findings demonstrate processing function.Significance Statement This first study show womb results circuitry, last We also show, for time, different, synapses different areas.