Prenatal opioid exposure: The next neonatal neuroinflammatory disease

Abstract

The rates of opioid use disorder during pregnancy have more than quadrupled in the last decade, resulting in numerous infants suffering exposure to opioids during the perinatal period, a critical period of central nervous system (CNS) development. Despite increasing use, the characterization and definition of the molecular and cellular mechanisms of the long-term neurodevelopmental #

Neonatal Hypoxic-Ischemic Encephalopathy Yields Permanent Deficits in Learning Acquisition: A Preclinical Touchscreen Assessment

“…Both groups performed at equivalent levels during reversal sessions when performance was low and perseveration high (i.e., <50%), while HIE mice committed more trials and errors during sessions when performance was largely learning related (i.e., >50%). This deficit is in contrast to previously published touchscreen assessments in animal models of perinatal brain injury (38,41,57). Specifically, adult rats perinatal brain injury secondary to chorioamnionitis have a perseverative phenotype and significant deficit in cognitive control defined by a reversal deficit (38).…”

“…The extensive white matter brain injury and orbitofrontocortical decoupling observed in both chorioamnionitis and traumatic brain injury may partially explain these findings. Interestingly, animals with perinatal exposure to methadone have a mixed phenotype of executive dysfunction with rats committing significantly more correction errors both during the perseverative phase and during the later learning phase compared to saline control animals (57). Together, these data indicate that adult rats exposed to perinatal methadone are impaired in both early and late reversal learning, consistent with global learning and executive control dysfunction (57) and widespread structural brain injury.…”

“…Interestingly, animals with perinatal exposure to methadone have a mixed phenotype of executive dysfunction with rats committing significantly more correction errors both during the perseverative phase and during the later learning phase compared to saline control animals (57). Together, these data indicate that adult rats exposed to perinatal methadone are impaired in both early and late reversal learning, consistent with global learning and executive control dysfunction (57) and widespread structural brain injury. In contrast to methadone exposure, prenatal alcohol exposure in mice results in behavioral inflexibility during early reversal testing, with persistent aberrant lateral orbital frontal cortex to dorsolateral striatum signaling (58).…”

Prenatal Methadone Exposure Disrupts Behavioral Development and Alters Motor Neuron Intrinsic Properties and Local Circuitry

“…Others also reported an accumulation of methadone in the rodent fetal brain 41 . We added to these findings by demonstrating methadone accumulated in The persistent decrease in the size of offspring was striking, and other models of prenatal opioid exposure, including methadone, similarly demonstrated reduced body weight 13,17,18 . In humans, prenatal opioid exposure is similarly associated with low birth weight and being small for gestational age 43 sensorimotor activity.…”

“…Animal models of prenatal opioid exposure have demonstrated deficits in several sensorimotor milestones [12][13][14] , but the mechanisms underlying disrupted sensorimotor development are unclear. Preclinical studies suggest that prenatal opioid exposure may prevent normal neuronal development 15,16 and disturb myelination 17 which could underlie the aberrant neurobehavioral development. Unfortunately, the translational value of these rodent studies is limited by models that do not adequately model the majority of human prenatal opioid exposure cases.…”