EARLY HYPOTHALAMIC ACTIVATION OF COMBINED FOS AND CRH41 IMMUNOREACTIVITY AND OF CRH41 RELEASE IN PUSH-PULL CANNULATED RATS AFTER SYSTEMIC ENDOTOXIN CHALLENGE

We previously showed that intra-arterial endotoxin infusion (lipopolys accharide [LPS]: 25 mu g . kg(-1)) induced an early (15 min) and susta ined (480 min) rise in plasma ACTH associated with delayed (60-120 min ) increases in plasma concentrations of TNF alpha, IL-6, and IL-1 beta . In the present study, we followed the post-LPS time-course of immuno cytochemical expression of Fos-like activity in CRH41 neurons whose im munolabeling was enhanced by icy colchicine pretreatment 48 h before t he LPS, and CRH41 release in the push-pull cannulated median eminence of free-moving rats, in parallel with the ACTH response. The earliest Fos-like activity in IR-CHR41 neurons was detected 30 min post-LPS. Co lchicine strongly inhibited the LPS-induced activation of Fos expressi on in single-labeled paraventricular neurons. CRH41 release in the med ian eminence displayed a biphasic stimulation pattern, with a first pe ak (+ 60%) at 15 min together with the ACTH surge, followed by a secon d rise beginning at 45 min and lasting more than 2 h. Thus, the early stage of the ACTH surge following a nonlethal endotoxin challenge (< 6 0 min) already involves the activation of CRH41-producing neurons.