Neonatal Hypoxia Induces Behavioral Deficit Associated with Impairment in the Glucocorticoid and Serotonergic Systems in Adult Rats

We investigated the behavioral responses, raphe serotonin levels, and serum concentrations of adrenocorticotropic hormone (ACTH), corticosterone, and serotonin in adult rats subjected to three sessions of hypobaric hypoxia (360 mmHg, 2 hours each) within 8-10 days post-partum. This non-invasive rat model of neonatal hypoxia (NH) simulates mild perinatal hypoxic trauma in fetuses and premature infants. At 3 months of age, NH-exposed rats exhibited reduced exploratory behavior and increased anxiety in both the open field and plus maze tests. These behavioral changes were accompanied by decreased serotonin levels in the raphe nuclei. In the blood serum of adult NH-exposed rats, corticosterone and serotonin levels remained unaltered, while ACTH levels showed a significant decrease. Our findings suggest that early postnatal hypoxic stress disrupts the serotonin system and alters HPA axis function, leading to long-lasting behavioral changes.