Neonatal handling is an experimental paradigm for early experiences. It affects the programming of hypothalamo-pituitary-adrenal (HPA) axis function, known to be sexually dimorphic. Recently leptin, a hormone related to energy balance and secreted mainly by adipocytes, has been implicated in the stress response. We thus determined the effect of neonatal handling on plasma concentrations of corticosterone and leptin of male and female rats under basal conditions and after two consecutive chronic stressors: chronic forced swimming stress and chronic restraint. Handling resulted in lower basal corticosterone levels in both males and females and in a more efficient HPA response, with a large corticosterone surge following the first chronic stressor and a return to basal levels following the second. Handling also resulted in decreased plasma leptin concentrations in males, thus abolishing the sex difference in leptin levels. Furthermore, handling increased body weight while it decreased food intake under basal conditions. Food intake and body weight gain during chronic forced swimming was lower in handled than in non-handled males, while in females these parameters were not influenced by handling. In both males and females, handling resulted in decreased food intake and increased body weight loss during chronic restraint stress. Body weight loss during chronic restraint stress, which is considered an index of maladaptation and ‘depression’, was particularly pronounced in the handled females. Our results also showed that non-handled females had higher corticosterone and lower leptin levels than males under basal conditions and following each of the two chronic stressors. The present work suggests that early experiences, such as the mother–infant relationship, interact with endogenous factors, such as gonadal hormones, to determine the organism’s response to stressful stimuli during adulthood.

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