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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Serotonergic mechanisms on breathing modulation in the rat locus coeruleus

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Author(s):
Moreno, Vanessa de Souza [1] ; Bicego, Kenia C. [1] ; Szawka, Raphael E. [2] ; Anselmo-Franci, Janete A. [2] ; Gargaglioni, Luciane H. [3, 1]
Total Authors: 5
Affiliation:
[1] Sao Paulo State Univ, UNESP FCAV, Dept Anim Morphol & Physiol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Morphol Stomatol & Physiol, Dent Sch Ribeirao Preto, Sao Paulo - Brazil
[3] Univ Estadual Paulista, Fac Ciencias Agr & Vet, Dept Morfol & Fisiol Anim, BR-14870000 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY; v. 459, n. 3, p. 357-368, FEB 2010.
Web of Science Citations: 15
Abstract

The locus coeruleus (LC) is a noradrenergic nucleus that plays an important role in the ventilatory response to hypercapnia. This nucleus is densely innervated by serotonergic fibers and contains high density of serotonin (5-HT) receptors, including 5-HT(1A) and 5-HT(2). We assessed the possible modulation of respiratory response to hypercapnia by 5-HT, through 5-HT(1A) and 5-HT(2) receptors, in the LC. To this end, we determined the concentrations of 5-HT and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) in the LC after hypercapnic exposure. Pulmonary ventilation (V(E), plethysmograph) was measured before and after unilateral microinjection (100 nL) of WAY-100635 (5-HT(1A) antagonist, 5.6 and 56 mM), 8-OHDPAT (5-HT(1A/7) agonist, 7 and 15 mM), Ketanserin (5-HT(2A) antagonist, 3.7 and 37 mM), or (+/-)-2,5-dimethoxy-4-iodoamphetaminehydrochloride (DOI; 5-HT(2A) agonist, 6.7 and 67 mM) into the LC, followed by a 60-min period of 7% CO(2) exposure. Hypercapnia increased 5-HTIAA levels and 5-HIAA/5-HT ratio within the LC. WAY-100635 and 8-OHDPAT intra-LC decreased the hypercapnic ventilatory response due to a lower tidal volume. Ketanserin increased CO(2) drive to breathing and DOI caused the opposite response, both acting on tidal volume. The current results provide evidence of increased 5-HT release during hypercapnia in the LC and that 5-HT presents an inhibitory modulation of the stimulatory role of LC on hypercapnic ventilatory response, acting through postsynaptic 5-HT(2A) receptors in this nucleus. In addition, hypercapnic responses seem to be also regulated by presynaptic 5-HT(1A) receptors in the LC. (AU)