ROLE OF INTRAPREOPTIC NOREPINEPHRINE IN ENDOTOXIN-INDUCED FEVER IN GUINEA-PIGS

The peripheral administration of pyrogens has been shown previously to affect the activity of central noradrenergic neurons, but the effects have been variable and no consensus has emerged regarding their funct ional significance. Because norepinephrine (NE) microdialyzed into the preoptic area (PO) of the anterior hypothalamus of conscious guinea p igs is hypothermizing, the possibility was investigated whether NE mig ht be a febrilytic rather than a febrigenic mediator. Intravenous inje ctions of Salmonella enteritidis lipopolysaccharide (2.0 mug/kg) evoke d a bimodal fever, which was attenuated in a dose-dependent manner by NE microdialyzed (10 or 20 mug/mul at a rate of 2 mul/min for various durations) into the PO. The alpha2-adrenergic receptor antagonists rau wolscine (1 or 2 mug/mul) and yohimbine (1 mug/mul) microdialyzed intr apreoptically significantly reduced the trough of body (core) temperat ure (T(c)) between the first and second peaks of the bimodal fever and prolonged the overall febrile course. None of these effects was assoc iated with changes in skin temperature. The level of NE (assayed by hi gh-performance liquid chromatography with electrochemical detection) i n the preoptic extracellular fluid collected by intracerebral microdia lysis was significantly elevated at the end of each rising phase of th e bimodal fever, just before or about the tune when T(c) began to fall , compared with pyropyrogen-free saline controls at the same times. Th ese results suggest that intrapreoptic NE may have a thermolytic effec t on fever by reducing metabolic heat production and may thus play a p hysiological role in the initiation of febrilysis in guinea pip.