1. Serotonergic mechanisms on breathing modulation in the rat locus coeruleus
- Author
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Kênia C. Bícego, Vanessa de Souza Moreno, Raphael E. Szawka, Luciane H. Gargaglioni, and Janete Aparecida Anselmo-Franci
- Subjects
Male ,Agonist ,Serotonin ,medicine.medical_specialty ,Ketanserin ,Microinjections ,Pyridines ,Physiology ,medicine.drug_class ,Clinical Biochemistry ,Serotonin 5-HT1 Receptor Antagonists ,Serotonergic ,Piperazines ,Hypercapnia ,Idazoxan ,Postsynaptic potential ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Receptor, Serotonin, 5-HT2A ,Rats, Wistar ,Adrenergic alpha-Antagonists ,Tidal volume ,8-Hydroxy-2-(di-n-propylamino)tetralin ,Chemistry ,Respiration ,Amphetamines ,Hydroxyindoleacetic Acid ,Serotonin 5-HT1 Receptor Agonists ,Rats ,Serotonin Receptor Agonists ,Endocrinology ,Receptor, Serotonin, 5-HT1A ,Serotonin 5-HT2 Receptor Antagonists ,Locus coeruleus ,Locus Coeruleus ,Serotonin Antagonists ,medicine.symptom ,Pulmonary Ventilation ,Serotonin 5-HT2 Receptor Agonists ,medicine.drug - 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 (VE: , 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.
- Published
- 2009
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