%0 Journal Article %A Jason Bondoc Alipio %A Lace Marie Riggs %A Madeline Plank %A Asaf Keller %T Environmental enrichment mitigates the long-lasting sequelae of perinatal fentanyl exposure %D 2021 %R 10.1101/2021.07.31.454575 %J bioRxiv %P 2021.07.31.454575 %X The opioid epidemic is a rapidly evolving societal issue that stems from the use of prescription and illicit opioids, including increasing use of synthetic opioids like fentanyl. Fentanyl use among women has increased substantially in the last decade, leading to a 40-fold increase in the number of perinatally-exposed infants. This exposure can result in neuropsychiatric abnormalities that persist into adolescence and, in some cases, adulthood. We previously developed a preclinical model to establish the consequences of perinatal fentanyl exposure and identified a pattern of synaptic pathophysiology that involves lasting impairments in primary somatosensory (S1) circuit function and behavior. Here, we ask if these long-lasting effects can be restored by a non-invasive intervention. We demonstrate that developmental exposure to environmental enrichment ameliorates many of fentanyl’s deleterious behavioral effects, including hyperactivity, enhanced sensitivity to anxiogenic environments, and sensory maladaptation in C57BL/6J mice. As an extension of our past work, we find that perinatal fentanyl alters the frequency of miniature excitatory postsynaptic currents and impairs long-term potentiation in S1 layer 2/3 neurons. These deficits in synaptic function were restored by environmental enrichment. Environmental enrichment also affected neurons in control mice, reducing long-term potentiation and depression, and increasing frequency of miniature excitatory postsynaptic currents. These results demonstrate that the lasting effects of fentanyl can be ameliorated with a non-invasive intervention introduced during early development. These findings can inform efforts to mitigate the consequences of opioid use among pregnant women.Significance Statement Children and adolescents exposed to opioids during perinatal development have a higher risk of developing neuropsychiatric disorders. Here, we employ a preclinical model of perinatal fentanyl exposure that recapitulates these long-term impairments, and show that environmental enrichment can reverse deficits in somatosensory circuit function and behavior when introduced early in postnatal development. These findings have the potential to directly inform and guide ongoing efforts to mitigate the consequences of perinatal opioid exposure.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2021/10/13/2021.07.31.454575.full.pdf