Maternal morphine exposure during lactation alters hippocampal morphology and Oprm1 expression in rat offspring: An experimental study

Background: Maternal morphine use during lactation may affect neonatal brain development through drug transfer into breast milk. Objective: To investigate the effects of short-term maternal morphine exposure during lactation on hippocampal morphology and neurodevelopment-related gene expression in rat offspring. Materials and Methods: This experimental study was conducted at Mazandaran University of Medical Sciences, Ramsar Campus, Ramsar, Iran in 2025. Adult lactating Sprague-Dawley rats (210–240 gr, 2–4 months) were randomly assigned to either the control or morphine-treated group. Lactating female rats in the treatment group received morphine sulfate (10 mg/kg, intraperitoneally) on postnatal days 4 and 5, whereas control animals received normal saline. On postnatal day 12, hippocampal tissues from their offspring (n = 6/group) were collected for histological, immunohistochemical, and quantitative reverse transcription polymerase chain reaction analyses. Immunohistochemical assessment included glial fibrillary acidic protein, S100 calcium-binding protein, and synaptophysin. Gene expression levels of neuronal differentiation-1, synaptophysin, neurexin-1, and opioid receptor Mu 1 were quantified using the ΔΔCt-2 method. Results: Histological examination revealed qualitative evidence of neuronal degeneration and inflammatory cell accumulation in the hippocampus of morphine-exposed offspring. Analysis demonstrated reduced immunoreactivity for glial fibrillary acidic protein, S100, and synaptophysin immunoreactivity compared with controls. Gene expression analysis showed a significant reduction in Oprm1 expression (p = 0.0176). Although other genes examined exhibited lower mean expression levels in the morphine-exposed group, these differences did not reach statistical significance. Conclusion: Short-term maternal morphine exposure during lactation was associated with hippocampal histopathological alterations and reduced Oprm1 expression in rat offspring. Further studies are needed to confirm these findings.