Sex-dependent behavioral and hypothalamic receptor changes after early-life monosodium glutamate (MSG) exposure and adult social stress in Wistar rats

Obesity is a growing public health issue, with comorbidities including metabolic syndrome and psychiatric disorders. Stress, an inherent factor in daily life, can influence mood and eating behavior and contribute to psychiatric diseases. This study investigated whether social-single prolonged stress (social-SPS) affects anxiety-like and eating patterns in male and female rats exposed to an early-life monosodium glutamate (MSG)-induced obesity model. We also evaluated changes in hypothalamic protein expression levels of leptin (Ob-R), ghrelin (GHS-R1), dopamine 1 (D1R), and dopamine 2 (D2R) receptors. Male and female Wistar rats were exposed to MSG (4 g/kg/day) from post-natal day (PND) 1 to 10, followed by social-SPS exposure at PND 60. Rats were euthanized on PND 69, and hypothalamic samples were analyzed. MSG increased the Lee Index in both sexes at PND 60. MSG-treated rats exhibited reduced cumulative water, as well as decreased body weight over time. Cumulative food intake decreased only in male MSG-treated rats. Both MSG and Social-SPS, when used independently and in combination, reduced food intake in both sexes. Additionally, MSG and Social-SPS individually induced anxiety-like behavior only in females, but did not affect locomotor parameters in both sexes. Male rats exhibited decreased hypothalamic GHS-R1/Ob-R/D2R receptor protein expression, while females showed decreased Ob-R/D1R. These molecular changes were positively correlated with behavioral outcomes. These findings indicate that social-SPS can affect anxiety-like phenotype, eating patterns, and molecular responses in a sex-dependent manner within an early-life obesity model induced by MSG.