title: Role of an excitatory preoptic-raphé pathway in febrile vasoconstriction of the rat's tail.
abstract: Heat dissipation from the rat's tail is reduced in response to cold and during fever. The sympathetic premotor neurons for this mechanism, located in the medullary raphé, are under tonic inhibitory control from the preoptic area. In parallel with the inhibitory pathway, an excitatory pathway from the rostromedial preoptic region (RMPO) to the medullary raphé mediates the vasoconstrictor response to cold skin. Whether this applies also to the tail vasoconstrictor response in fever is unknown. Single- or a few-unit tail sympathetic nerve activity (SNA) was recorded in urethane-anesthetized, artificially ventilated rats. Experimental fever was induced by PGE2 injected into the lateral cerebral ventricle (50 ng in 1.5 μl icv) or into the RMPO (0.2 ng in 60 nl); in both cases, there was a robust increase in tail SNA and a delayed rise in core temperature. Microinjection of glutamate receptor antagonist kynurenate (50 mM, 120 nl) into the medullary raphé completely reversed the tail SNA response to intracerebroventricular or RMPO PGE2 injection. Inhibiting RMPO neurons by microinjecting glycine (0.5 M, 60 nl) or the GABAA receptor agonist, muscimol (2 mM, 30-60 nl), reduced the tail SNA response to PGE2 injected into the same site by approximately half. Vehicle injections into the medullary raphé or RMPO were without effect. These results suggest that the tail vasoconstrictor response during experimental fever depends on a glutamatergic excitatory synaptic relay in the medullary raphé and that an excitatory output signal from the RMPO contributes to the tail vasoconstrictor response during fever.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia;
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKinley
authors.forename: Robin M
authors.initials: RM
authors.lastname: McAllen
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000009:adverse effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D005998:Glycine / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D023421:Models, Animal; D009118:Muscimol / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D013623:Tail / Q000098:blood supply* / Q000294:innervation* / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D009118:Muscimol; D007736:Kynurenic Acid; D015232:Dinoprostone; D005998:Glycine
keywords: glycine; kynurenate; prostaglandin E2