Gestational buprenorphine exposure disrupts dopamine neuron activity and related behaviors in adulthood.

Opioid misuse among pregnant women is rapidly increasing in the United States. The number of maternal opioid-related diagnoses increased by 131% in the last ten years, resulting in an increased number of infants exposed to opioids in utero and a subsequent increase in infants developing neonatal abstinence syndrome (NAS). The most prescribed treatment to combat maternal opioid use disorder is buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist. Buprenorphine treatment effectively reduces NAS but has been associated with disrupted cortical development and neurodevelopmental consequences in childhood. Less is known about the long-term neurodevelopmental consequences following buprenorphine exposure in utero Previous research has shown that gestational buprenorphine exposure can induce anxiety- and depressive-like phenotypes in adult rats, suggesting that exposure to buprenorphine in utero may render individuals more susceptible to psychiatric illness in adulthood. A common pathology observed across multiple psychiatric illnesses is dopamine system dysfunction. Here, we administered the highly-abused opioid, oxycodone (10 mg/kg, i.p.) or a therapeutic used to treat opioid use disorder, buprenorphine (1 mg/kg, i.p) to pregnant Sprague Dawley rats from gestational day 11 through 21, then examined neurophysiological alterations in the mesolimbic dopamine system and dopamine-dependent behaviors in adult offspring. We found that gestational exposure to buprenorphine or oxycodone increases dopamine neuron activity in adulthood. Moreover, prenatal buprenorphine exposure disrupts the afferent regulation of dopamine neuron activity in the ventral tegmental area (VTA). Taken together, we posit that gestational buprenorphine or oxycodone exposure can have profound effects on the mesolimbic dopamine system in adulthood. Significance Statement The opioid epidemic in the United States is a growing problem that affects people from all demographics, including pregnant women. In 2017, nearly 21,000 pregnant women reported misusing opioids during pregnancy, which can lead to many physiological and neurodevelopmental complications in infants. To combat illicit opioid use during pregnancy, buprenorphine is the priority treatment option, as it reduces illicit opioid use and alleviates symptoms of neonatal abstinence syndrome in infants. However, less is known about the long-term neurophysiological consequences of in utero opioid or buprenorphine exposure. Here, we demonstrate that both oxycodone and buprenorphine exposure, in utero , can result in aberrant dopamine system function in adult rats. These results provide evidence of potential long-lasting effects of opioid exposure during development.