Prenatal opioid exposure (POE) is associated with abnormal brain structure and functioning in affected individuals, underscoring a need for preclinical models to discover the neuro-molecular origins of such deficits. Rodent models can recreate the developmental impacts of POE across all three trimesters by exposing offspring at equivalent brain stages before and after birth. However, studies using rodent models vary regarding whether prenatal, postnatal, or even pre-mating exposure are included. Without understanding how exposure timing influences brain changes, the findings of rodent models cannot be disentangled from the specific exposure regimes used, and clinically useful mechanisms for brain abnormalities cannot be identified. Thus, this review examines whether variation in opioid exposure timing in rodent POE models influences the cellular and molecular biology of the developing brain. Prenatal exposure across mid-to-late gestation reliably stunts neurogenesis and GABAergic synapse formation, and may activate glial inflammatory processes, regardless of onset. Postnatal exposure alone contributes less to synapto- and oligodendrogenesis, and astrocyte and microglial formation, than prenatal followed by postnatal exposure in the first two weeks. Overall, small variations in onset and cessation points are less critical than the choice to broadly expose offspring before or after birth. Exposure during the critical windows of mid-to-late gestation, and early postnatal life, are thus most important for rodent POE models aiming to replicate aetiologies of neuronal and glial developmental abnormality, generate long-term predictions, and improve translatability of results. • Variations in timing of rodent prenatal opioid exposure limits translatability • Mid-to-late gestational exposure disturbs neuronal, synaptic and glial genesis • Postnatal exposure alters synapse and myelin formation, astrocytes and microglia • Postnatal exposure alone is insufficient to alter most neurodevelopmental outcomes • Perinatal exposure best recapitulates human opioid-induced neurobiological changes
Soengkoeng et al. (Wed,) studied this question.