Perinatal opioid exposure alters alcohol-driven reward behaviors in adolescent male and female rats.

In the U.S., a baby is born with neonatal opioid withdrawal syndrome (NOWS) every 15 min-a rate that has increased sevenfold since 2004. Clinical studies have established intrauterine exposure to addictive drugs as a risk factor for adverse health outcomes in adolescence, including increased propensity for future illicit drug use. Despite extensive knowledge regarding common mechanisms of action in the neural circuitry that drives opioid and alcohol reward, there are limited data on the risks infants with NOWS face regarding alcohol use later in life. Our laboratory has developed a clinically relevant model for morphine exposure in rats spanning pre-conception to the first postnatal week. Using this model, we report that perinatal opioid exposure (POE) increased alcohol consumption in female rats under home cage conditions and, inversely, reduced alcohol consumption in both male and female rats in an operant conditioning paradigm. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to addictive drugs. Parallel studies examined the effect of perinatal morphine exposure on μ-opioid receptor (MOR) expression in male and female rats at postnatal and adolescent ages. We report age and region-dependent changes in MOR within the nucleus accumbens and medial habenula, regions previously shown to play significant roles in reward/aversion circuitry. Together, our results provide novel evidence of changes in alcohol-directed reward behavior in a clinically relevant rat model of perinatal opioid exposure.