SODIUM BUTYRATE RESCUES PRENATAL OPIOID INDUCED GUT, IMMUNE AND COGNITIVE DYSFUNCTION: IDENTIFYING CRITICAL WINDOWS FOR INTERVENTION

Aims: Opioid exposure during pregnancy causes serious long-term neurodevelopmental and neuropsychiatric deficits in offspring, with no available treatments. We previously showed that perinatal sodium butyrate (NaB) reverses some prenatal opioid-induced deficits in rats, but treatment in pregnancy is not clinically feasible. Here we compared the benefits of prenatal vs postnatal NaB administration.
Methods: 37 pregnant rat dams received methadone via mini-osmotic pump and/or NaB in drinking water. NaB was administered either to model human prenatal neurodevelopment (prenatal) or after birth into adolescence (postnatal). Gut barrier and immune function were assessed in infancy (PND9) and adolescence (PND33), and cognition and impulsivity were tested in adulthood.
Results: Prenatal methadone disrupted the gut barrier at PND9, which was prevented by prenatal NaB. Both prenatal methadone and prenatal NaB reduced spleen weight, while prenatal NaB increased relative brain weight. Both treatments shifted immune responsivity, with all early changes resolving by PND33. Postnatal NaB normalized methadone-induced deficits in impulsivity in males, while prenatal NaB improved spatial pattern recognition in females.
Conclusions: NaB provides time-dependent protection following prenatal methadone exposure. Prenatal NaB prevents methadone-induced gut and immune dysfunction in infancy and increases relative brain size, which is associated with improved spatial cognition in female offspring in adulthood. In contrast, postnatal NaB selectively improved impulsivity in males. These data highlight the importance of matching treatment timing to the critical developmental windows of vulnerable systems to maximise therapeutic benefit after prenatal opioid exposure.