Agrawal_2025_Psychopharmacology.(Berl)__

RATIONALE: Antidepressant (AD) use during pregnancy raises concerns regarding its potential impact on offspring neurodevelopment. Vilazodone (VLZ), a newer AD with a favourable therapeutic profile, remains underexplored in this context. OBJECTIVES: This study aimed to investigate the effects of prenatal VLZ exposure on hippocampal neurochemistry and cognitive function in young adult rat offspring. METHODS: Pregnant Wistar rats received VLZ (1 or 2 mg/kg/day) via a cannula from gestational day 6 to 21. After delivery, offspring were reared until postnatal day (PND) 70. Postnatal body weight (PND 1-70) and behavioural performances (PND 49-70) were evaluated in six (n=6) offspring/sex/group (one male and one female per litter) using the Morris water maze and step-down passive avoidance tests. Sex was initially included as a factor in the statistical analysis; as no significant sex differences were observed, data were pooled for molecular and histological analyses (n=6 brains/group; 3 males and 3 females). RESULTS: Offspring prenatally exposed to VLZ exhibited reduced body weight, impaired spatial and avoidance learning, and altered hippocampal morphology compared to the controls. Biochemical and molecular analyses of the hippocampus revealed reduced levels of brain-derived neurotrophic factor (BDNF), an elevated Bax/Bcl-2 ratio, and increased acetylcholinesterase activity. These effects were significant at 2 mg/kg, with no notable changes at 1 mg/kg. CONCLUSIONS: Prenatal exposure to 2 mg/kg VLZ disrupts neurodevelopment, resulting in persistent cognitive deficits and hippocampal alterations. These findings highlight the need for caution when prescribing VLZ during pregnancy, particularly during crucial phases of fetal brain development.