Effects of Post-Conceptional Melatonin on Cerebral Cortex Alterations in Offspring of Prenatal Valproate-exposed Wistar Rats

Abstract The effects of post-conceptional melatonin administration on prenatal-sodium valproate (SV)- induced changes in behaviour and cerebral cortex histomorphology in rats were examined in this study. Twenty-five rats (150–200 g) were mated with age-matched males and pregnancy confirmed by presence of vaginal plug. Pregnant dams were assigned into five groups. group A (Control) administered distilled water (10 ml/kg) and intraperitoneal (i.p) injection of saline (2ml/kg), B SV control, received distilled water and i.p SV (150 mg/kg). Groups C-E were administered i.p SV and melatonin (5, 10, and 20 mg/kg) via oral gavage. Distilled water and melatonin were administered from post conceptional day (PCD) 1–10, while single i.p injection of saline and SV was administered on PCD 12. Pregnant dams delivered on PCD 21 and cared for their offspring till weaned on postnatal day (PND) 21. Weaned rat pups were exposed to behavioural paradigms (open-field arena, social interaction test, elevated plus maze and Y-maze) on PND 35. On PND 36, pups were euthanized, and brains were processed for general histology. Results showed a decrease in self grooming, spatial memory and social interaction while an increase in locomotor activity and rearing was observed with SV. Post-conceptional melatonin increased, self-grooming, spatial memory and social interaction and decreased rearing and locomotor activity. Administration of SV caused neuronal loss in the cerebral cortex, while melatonin was associated with protection against SV-induced neuronal injury. In conclusion, melatonin mitigated against maternal SV-induced behavioural and structural changes in the cerebral cortex of offspring.