The central amygdala modulates hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1β administration

In the present study we examined the role of the central nucleus of the amygdala in hypothalamic-pituitary-adrenal axis responses to an immune challenge in the form of systemic administration of the proinflammatory cytokine interleukin-1 beta (1 mu g/kg). We found that bilateral ibotenic acid lesions of the central amygdala substantially reduced adrenocorticotropin hormone release and hypothalamic corticotropin-releasing factor and oxytocin cell c-fos expression responses to interleukin-1 beta suggesting a facilitatory role for this structure in the generation of hypothalamic-pituitary-adrenal axis responses to an immune challenge. Since only a small number of central amygdala cells project directly to the paraventricular nucleus, we then examined the effect of central amygdala lesions on the activity of other brain nuclei that might act as relay sites in the control of the hypothalamic-pituitary-adrenal axis function. We found that bilateral central amygdala lesions significantly reduced interleukin-1 beta-induced c-fos expression in cells of the ventromedial and ventrolateral subdivisions of the bed nucleus of the stria terminalis and brainstem catecholamine cell groups of the nucleus tractus solitarius (A2 noradrenergic cells) and ventrolateral medulla (A1 noradrenergic and C1 adrenergic cells). These findings, in conjunction with previous evidence of bed nucleus of the stria terminalis and catecholamine cell group involvement in hypothalamic-pituitary-adrenal axis regulation, suggest that ventromedial and ventrolateral bed nucleus of the stria terminalis cells and medullary catecholamine cells might mediate the influence of the central amygdala on hypothalamic-pituitary-adrenal axis responses to an immune challenge. Thus these data establish that the central amygdala influences hypothalamic-pituitary-adrenal axis responses to a systemic immune challenge but indicate that it primarily acts by modulating the activity of other control mechanisms. (C) 1999 IBRO. Published by Elsevier Science Ltd.