Serotonergic mechanisms on breathing modulation in the rat locus coeruleus

Autor(es)

Moreno, Vanessa de Souza ^[1] ; Bicego, Kenia C. ^[1] ; Szawka, Raphael E. ^[2] ; Anselmo-Franci, Janete A. ^[2] ; Gargaglioni, Luciane H. ^{[3, 1]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY; v. 459, n. 3, p. 357-368, FEB 2010.
• Citações Web of Science: 15

Resumo

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)

• Processo FAPESP: 05/56128-9 - Participação da neurotransmissão serotoninérgica no locus coeruleus na hiperventilação e na hipotermia induzidas por hipercapnia
• Beneficiário: Vanessa de Souza Moreno
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica