THE CNS SITE OF GLUCOCORTICOID NEGATIVE FEEDBACK DURING LPS-INDUCED AND PSYCHOLOGICAL STRESS-INDUCED FEVERS

Glucocorticoids exert negative feedback in the anterior hypothalamus ( AH) during lipopolysaccharide (LPS)-induced fevers, but the central lo cation of their negative feedback during psychological stress-induced fever has not been determined. To confirm that glucocorticoid modulati on of LPS fever occurs in the AH, adrenalectomized animals were inject ed intrahypothalamically with either 0.25 ng of corticosterone or vehi cle followed by 50 mu g/kg LPS intraperitoneally. Animals pretreated w ith corticosterone developed significantly smaller fevers (P = 0.007) than animals given vehicle. To determine if glucocorticoid modulation during psychological stress-induced fever may occur in the hippocampus , the fornix was transected to block hippocampal communication with th e AH. This resulted in significantly larger psychological stress-induc ed fevers (P = 0.02) compared with sham-operated animals. There were n o differences between these groups for LPS-induced fevers (P = 0.92). To determine where in the hippocampus glucocorticoids might exert thei r negative feedback during psychological stress, rats were microinject ed with either 1 ng RU-38486 (a type II glucocorticoid receptor antago nist) or vehicle into the dentate gyrus prior to exposure to the open field. There were no differences between the psychological stress-indu ced fevers of the RU-38486- and vehicle-injected groups, supporting th e hypothesis that these fevers are modulated elsewhere in the hippocam pus. Our data support the hypothesis that glucocorticoids modulate LPS -induced fever in the AH and do not involve the hippocampus, and that psychological stress-induced fevers are modulated by neural connection s between the hippocampus and the hypothalamus. The precise sites of a ction of glucocorticoid negative feedback. on stress-induced fevers in the hippocampus (or other brain regions) are not yet known.