Advances in animal models of prenatal opioid exposure

Rates of neonatal opioid withdrawal syndrome (NOWS) have been increasing. Acute withdrawal symptoms are well characterized in NOWS infants, but environmental confounds and difficulties in conducting longitudinal studies make it challenging to elucidate potential long-term clinical effects.Preclinical animal models have great utility for studying the persisting consequences of perinatal opioid exposure and to address the mechanistic basis of these effects.Several preclinical perinatal opioid exposure models have been developed. Whereas early animal models primarily used the prototypical opioid, morphine, and a limited opioid exposure period, more recent models have been using various opioid types and different durations of perinatal opioid exposure.Behavioral phenotypes vary across models, reaffirming the importance of dosage, type of opioid, and duration of exposure for the development of specific phenotypes. Neonatal opioid withdrawal syndrome (NOWS) is a growing public health concern. The complexity of in utero opioid exposure in clinical studies makes it difficult to investigate underlying mechanisms that could ultimately inform early diagnosis and treatments. Clinical studies are unable to dissociate the influence of maternal polypharmacy or the environment from direct effects of in utero opioid exposure, highlighting the need for effective animal models. Early animal models of prenatal opioid exposure primarily used the prototypical opioid, morphine, and opioid exposure that was often limited to a narrow period during gestation. In recent years, the number of preclinical studies has grown rapidly. Newer models utilize both prescription and nonprescription opioids and vary the onset and duration of opioid exposure. In this review, we summarize novel prenatal opioid exposure models developed in recent years and attempt to reconcile results between studies while critically identifying gaps within the current literature. Neonatal opioid withdrawal syndrome (NOWS) is a growing public health concern. The complexity of in utero opioid exposure in clinical studies makes it difficult to investigate underlying mechanisms that could ultimately inform early diagnosis and treatments. Clinical studies are unable to dissociate the influence of maternal polypharmacy or the environment from direct effects of in utero opioid exposure, highlighting the need for effective animal models. Early animal models of prenatal opioid exposure primarily used the prototypical opioi