title: Alteration of locus coeruleus neuronal activity by interleukin-1 and the involvement of endogenous corticotropin-releasing hormone.
abstract: Activity of the locus coeruleus (LC), which is the source of most of the norepinephrine in the brain, may participate in effects of the cytokine interleukin (IL)-1. This report describes the influence of IL-1 beta on the electrophysiological single-unit activity of LC neurons. When microinjected into the LC, human recombinant IL-1 beta (50 pg to 5 ng) increased the activity of LC neurons, predominantly by increasing 'burst' firing, which occurs in response to a sensory stimulus. At the higher doses and/or with longer time delays after injection, the spontaneous depolarization rate was also increased. This excitation (1). did not occur if IL-1 beta was microinjected nearby but outside of the LC and (2). could be reversed by administration of IL-1 receptor antagonist (IL-1 RA). In contrast to excitatory effects, microinjection of a very low dose of IL-1 beta (5 pg) into the LC inhibited LC activity, and this change could also be blocked by IL-1 RA. In view of earlier findings that (1). LC electrophysiological activity could be inhibited by microinjection of corticotropin-releasing hormone (CRH) into the LC region and (2). IL-1 beta in the brain stimulates the release of CRH, the hypothesis was tested that the inhibition of LC activity produced by the low dose of IL-1 was mediated by CRH. Microinfusion of the CRH receptor antagonist alpha-helical CRH(9-41) blocked the inhibition of LC activity otherwise produced by 5 pg of IL-1 beta, thus indicating that IL-1 beta also influences the activity of LC neurons via CRH. Finally, microinjection of IL-1 RA alone was found to decrease LC activity, raising the possibility that LC neurons are under the influence of tonic excitation by IL-1 in the brain. In summary, the findings described here show that the activity of LC neurons can be influenced by IL-1 beta through stimulation of IL-1 beta receptors. The potential involvement of IL-1 beta in stress responses by means of this cytokine influencing the activity of LC neurons is discussed.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. mborsody@hotmail.com
authors.forename: Mark K
authors.initials: MK
authors.lastname: Borsody
authors.forename: Jay M
authors.initials: JM
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D007275:Injections, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D006727:Hormone Antagonists; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018722:Nicotinic Agonists; D010446:Peptide Fragments; D012795:Sialoglycoproteins; D009538:Nicotine; D002217:Carbachol; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)