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Serotonergic mechanisms on breathing modulation in the rat locus coeruleus
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Serotonergic mechanisms on breathing modulation in the rat locus coeruleus
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Journal Article
Serotonergic mechanisms on breathing modulation in the rat locus coeruleus
2010
Overview
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.
Publisher
Springer-Verlag,Springer Nature B.V
Subject
8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
/ Adrenergic alpha-Antagonists - pharmacology
/ Animals
/ Biomedical and Life Sciences
/ Hydroxyindoleacetic Acid - metabolism
/ Locus Coeruleus - drug effects
/ Locus Coeruleus - metabolism
/ Male
/ Pulmonary Ventilation - physiology
/ Rats
/ Receptor, Serotonin, 5-HT1A - metabolism
/ Receptor, Serotonin, 5-HT2A - metabolism
/ Serotonin 5-HT1 Receptor Agonists
/ Serotonin 5-HT1 Receptor Antagonists
/ Serotonin 5-HT2 Receptor Agonists
/ Serotonin 5-HT2 Receptor Antagonists
