Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms.

The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure (POE); however, the long-term effects of POE on offspring behavior and neurodevelopment remain relatively unknown. The advantages and disadvantages of the various preclinical POE models developed over the last several decades are discussed in the context of clinical and translational relevance. Although considerable and important variability exists among preclinical models of POE, the examination of these preclinical models has revealed that opioid exposure during the prenatal period contributes to maladaptive behavioral development as offspring mature including an altered responsiveness to rewarding drugs and increased pain response. The present review summarizes key findings demonstrating the impact of POE on offspring drug self-administration (SA), drug consumption, the reinforcing properties of drugs, drug tolerance, and other reward-related behaviors such as hypersensitivity to pain. Potential underlying molecular mechanisms which may contribute to this enhanced addictive phenotype in POE offspring are further discussed with special attention given to key brain regions associated with reward including the striatum, prefrontal cortex (PFC), ventral tegmental area (VTA), hippocampus, and amygdala. Improvements in preclinical models and further areas of study are also identified which may advance the translational value of findings and help address the growing problem of POE in clinical populations.