Role of corticosterone in the behavioral effects of central interleukin-1 beta.

To investigate the role of the hypothalamic-pituitary-adrenal (HPA) axis in behavioral responses to infection, we studied the effects of corticosterone on depressed social behavior induced by peripheral and central interleukin-1 beta (IL-1 beta) in the rat. Intact and adrenalectomized (ADX) rats were injected i.p. with IL-1 beta (500 ng) and their motivation to investigate a juvenile conspecific was assessed. Whereas ADX rats showed a marked depression in social behavior following i.p. IL-1 beta, intact controls did not. To verify that corticosterone was responsible for inhibiting the effects of IL-1 beta, corticosterone pellets or placebos were implanted i.p. in ADX rats. Following i.p. injection of IL-1 beta, ADX rats with placebos experienced depressed social behavior. Corticosterone replacement, however, reversed this effect in ADX rats, confirming that corticosterone modulates the behavioral effects of peripheral IL-1 beta. To determine if corticosterone modulates sickness behavior directly in the CNS, intact and ADX rats were injected i.c.v. with IL-1 beta or lipopolysaccharide (LPS). Although centrally administered IL-1 beta depressed social behavior to a similar extent in intact and ADX rats, the depression was prolonged in ADX rats. However, social behavior of ADX rats injected i.c.v. with LPS was depressed more than in intact controls, and this effect was reversible by corticosterone replacement. These results are interpreted to indicate that corticosterone inhibits the behavioral effects of IL-1 beta in the periphery and, perhaps, in the CNS. That the behavioral effects of central LPS were inhibited by corticosterone suggests the HPA axis may modulate behavior by regulating cytokine synthesis in the CNS.