title: Effect of subdiaphragmatic vagotomy on the noradrenergic and HPA axis activation induced by intraperitoneal interleukin-1 administration in rats.
abstract: The vagus nerve is thought to participate in signal transduction from the immune system to the CNS. The role of the vagus in the physiological, behavioral and neurochemical responses to intraperitoneally (ip) injected interleukin-1beta (IL-1beta) was studied using awake subdiaphragmatically vagotomized rats. The rats were injected ip with saline and IL-1beta (1 microg/rat) in random order. For the next 2-4 h, they were monitored for locomotor activity, body temperature via abdominally implanted telethermometers, hypothalamic norepinephrine (NE) secretion using in vivo microdialysis and blood sampled via intravenous catheters to determine concentrations of ACTH and corticosterone to assess hypothalamo-pituitary-adrenocortical (HPA) axis activation. Saline injections were followed by transient increases in locomotor activity, body temperature, dialysate NE and plasma concentrations of ACTH and corticosterone. These responses were not significantly altered by vagotomy. IL-1beta injections resulted in short-lived increases in shivering and longer decreases in locomotor activity, as well as a delayed modest fever. IL-1beta also induced prolonged elevations of hypothalamic microdialysate NE, as well as plasma ACTH and corticosterone. Similar responses were observed regardless of the order of the saline and IL-1beta injections. Subdiaphragmatic vagotomy prevented the IL-1-induced increases in body temperature and the increase in dialysate NE, and markedly attenuated the increases in plasma ACTH and corticosterone. The results indicate close temporal relationships between the apparent release of NE and the increase in body temperature and the HPA activation. This together with the effects of vagotomy suggests that the activation of NE in turn increases body temperature and activates the HPA axis. However, because IL-1beta induces a limited HPA activation in subdiaphragmatically vagotomized rats, the vagus nerve does not appear to be the only route by which ip IL-1beta can activate the HPA axis. It is suggested that IL-1beta-induced vagal activation of hypothalamic NE is the major mechanism of HPA activation at low doses of IL-1beta. However, IL-1beta can also exert direct effects on IL-1 receptors on cerebral blood vessels, activating cyclooxygenases and hence synthesis of prostaglandins which in turn can affect body temperature, behavior and HPA axis activation.
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, PO Box 33932, Shreveport, LA 71130-3932, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Wieczorek
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Dunn
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal / Q000379:methods; D007375:Interleukin-1 / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012768:Shivering / Q000187:drug effects; D014628:Vagotomy
chemical_list: D007375:Interleukin-1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D009638:Norepinephrine