Prevention of prolactin reduction: a novel strategy countering multi-generational growth retardation caused by maternal exposure to 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin

Neonatal growth and development are significantly influenced by maternal care and breastfeeding. Our previous research showed that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in dams reduced prolactin (PRL) levels, nursing behavior, and milk production during lactation. Intracerebroventricular infusion of PRL in TCDD-exposed dams partially reversed these defects in mothers and offspring. However, the mechanism by which maternal TCCD exposure causes reduced PRL levels and multigenerational effects remains unclear. This study aimed to investigate the multigenerational effects of maternal TCDD exposure and sought solutions to the developmental issues arising from low PRL levels due to TCDD exposure during gestation. Oral administration of TCDD (1 µg/kg) to pregnant rats on gestational day 15 (F₀ dams) led to decreased PRL concentrations in female offspring (F₁/F₂) and impaired maternal licking behavior when F₁ females had given birth, resulting in adverse effects on body weight and short-term memory in F₂/F₃ offspring. Aripiprazole (ARI), a partial dopamine D2 receptor (D2R) agonist, increases PRL levels by inhibiting the effect of dopamine during PRL synthesis and secretion. Importantly, administration of ARI to F₀ dams not only restored PRL levels, nursing behavior, and milk volume in the treated mothers but also mitigated the developmental deficits observed in F₂/F₃ offspring. These findings highlight the critical role of PRL in maternal care and offspring development and suggest that ARI could be a potential therapeutic intervention to mitigate the effects of TCDD-induced multi-generational developmental disruptions.