Serotonin reuptake inhibition does not enhance short term modulation of the exercise ventilatory response.
Increased respiratory dead space causes a serotonin (5-HT) dependent augmentation of the exercise ventilatory response known as short term modulation (STM). Contrary to predictions, 5-HT reuptake inhibition with fluoxetine failed to enhance, and even impaired STM with large dead space volumes (0.4-0.6 L). In this study, we tested the hypotheses that: (1) fluoxetine similarly impairs STM with smaller dead space volumes (0.2 L); whereas (2) acute 5-HT release and reuptake inhibition with fenfluramine would enhance STM. Ventilatory and blood gas measurements were made on five goats (37-58 kg) during rest and exercise, with the mask alone or with increased dead space (0.2 L). STM protocols were performed following chronic fluoxetine (>/=21 days, 1 mg/kg, SQ, SID) and acute fenfluramine administration (1 mg/kg, IV). Following fluoxetine, STM was partially impaired. Fenfluramine had no detectable effects on STM. The data suggest that: (1) chronic fluoxetine diminishes STM, possibly via down-regulation of relevant 5-HT receptors, and (2) drugs that release 5-HT acutely do not enhance STM.
Henderson
D R
DR
Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Dr. West Madison, WI 53706, USA. hendersd@svm.vetmed.wisc.edu
Konkle
D M
DM
Mitchell
G S
GS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005277:Fenfluramine / Q000493:pharmacokinetics / Q000494:pharmacology; D005473:Fluoxetine / Q000493:pharmacokinetics / Q000494:pharmacology; D006041:Goats; D005082:Physical Exertion / Q000502:physiology*; D012126:Respiratory Dead Space / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
D005277:Fenfluramine; D005473:Fluoxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors