Early-life environmental enrichment reduces anxiety and induces sex-dependent neuroplasticity in hypothalamic oxytocin and vasopressin neurons.

Early-life experiences critically shape neuroendocrine systems involved in emotional and social behaviours. The oxytocin (OXT) and vasopressin (AVP) systems are particularly sensitive to environmental influences during the perinatal period, a developmental window characterized by high neural plasticity. However, the long-term effects of perinatal environmental enrichment (PEE) on hypothalamic OXT and AVP neuroplasticity and their relationship with emotional behaviour remain poorly understood. Therefore, this study investigated whether PEE induces persistent behavioural, structural, and neurochemical changes in OXT and AVP neurons in male and female mice. Male and female mice reared in either PEE or non-enriched environment (NE) conditions were evaluated in adulthood using the elevated plus maze, light/dark box, and sociability/social novelty preference tests. Morphometric analyses assessed soma and nuclear size, as well as OXT and AVP immunoreactivity in neurons of the paraventricular nucleus (PVN) of the hypothalamus. PEE reduced anxiety-like behaviour, as evidenced by increased open-arm exploration in the elevated plus maze, particularly in males, and reduced latency to enter the light compartment in the light/dark box. These behavioural effects were accompanied by reduced soma and nuclear dimensions of AVP neurons in PEE males, as well as increased nuclear size and OXT immunoreactivity in both sexes. Correlation analyses showed that smaller AVP neuronal profiles were associated with reduced anxiety-related behavioural measures, whereas larger OXT neuronal dimensions were associated with reduced risk-assessment behaviours. Perinatal environmental enrichment induces long-lasting, sex-dependent structural and neurochemical plasticity in hypothalamic OXT and AVP systems, which may contribute to the enduring modulation of anxiety-related behaviours.