Corticosterone modulates behavioral and metabolic effects of lipopolysaccharide

The behavioral and neuroendocrine responses following infection are important mechanisms for maintaining homeostasis and promoting recovery. The purpose of this study was to determine if glucocorticoids modulate the behavioral and metabolic effects of lipopolysaccharide (LPS) in rats. A single injection of LPS (10 mu g/kg ip) increased plasma corticosterone at 4 h, but had no effect on social behavior, body temperature, or body weight. To determine if behavioral and metabolic effects of LPS were precluded by the increase in corticosterone, adrenalectomized (ADX) and sham-operated rats were injected with LPS. Whereas ADX rats expressed symptoms of sickness, intact controls did not. To verify that corticosterone was the adrenal hormone responsible for inhibiting these effects of LPS, corticosterone pellets or placebos were implanted intraperitoneally in ADX rats. Following injection of LPS, ADX rats with placebos expressed behavioral symptoms characteristic of sickness, including depressed social behavior. Corticosterone pellets, however, entirely reversed these effects in ADX rats. These results indicate that corticosterone modulates the behavioral and metabolic effects of LPS, suggesting that the hypothalamic-pituitary-adrenal axis is important in preventing profound behavioral disturbances in response to low-grade immune stimulation by infectious and noninfectious agents.