Download PDF
Int J Sports Med 2001; 22(5): 329-336
DOI: 10.1055/s-2001-15648
Physiology and Biochemistry

© Georg Thieme Verlag Stuttgart · New York

Exercise Performance is not Influenced by a 5-HT Reuptake Inhibitor

R. Meeusen, M. F. Piacentini, S. Van Den Eynde, L. Magnus, K.  De Meirleir
  • Vrije Universiteit Brussel
  • Department of Human Physiology and Sportsmedicine, Belgium
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Also available at
    Permissions and Reprints

The purpose of the present study was to examine the effect of a selective serotonin (5-HT) reuptake inhibitor (SSRI) on exercise performance during a 90 min time trial. Eight well trained male cyclists (V˙O2max 68.1 ± 9.5 ml/kg/min) performed three 90 min time trials at 65 % Wattmax. Blood samples were collected via an indwelling venous catheter for adrenocorticotropin hormone (ACTH), prolactin (PRL), cortisol, catecholamines, growth hormone (GH) and beta-endorphins. The evening before and the morning of the time trials, the subjects ingested a capsule containing either placebo (lactose) or 20 mg Fluoxetine-HCl (Prozac®, Ely Lilly Belgium). A double blind, randomized, placebo controlled, cross-over design was performed. Performance was not influenced by the SSRI. As expected, all blood parameters increased significantly during exercise (p < 0.05). During the SSRI trial most parameters were slightly lower but only significantly for endorphins and PRL (p < 0.05). The results demonstrate that performance is not influenced by an SSRI, although some plasma hormones indicate a central effect of the drug. Surprisingly, the increases in PRL and endorphins were lower during the SSRI trial, meaning that the hormonal modulation during exercise might be regulated by the interaction between neurotransmitters rather than by serotonin alone.

Key words:

Central fatigue, neurotransmitters, time trial, fluoxetine, serotonin.

References

  • 1 Acworth I, Nicolass J, Morgan B, Newsholme E A. Effect of sustained exercise on concentrations of plasma aromatic and branched chain amino acids and brain amines.  Biochem Biophys Res Comm. 1986;  137 149-153
    CrossrefPubMedGoogle Scholar
  • 2 Bailey S, Davis J, Ahlborn E. Effect of increased brain serotonergic activity on endurance performance in the rat.  Acta Physiol Scand. 1992;  145 75-76
    PubMedGoogle Scholar
  • 3 Bailey S, Davis J, Ahlborn E. Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue.  J Appl Physiol. 1993;  74 3006-3012
    PubMedGoogle Scholar
  • 4 Bailey S, Davis J, Ahlborn E. Serotonergic agonists and antagonists affect endurance performance in the rat.  Int J Sports Med. 1993;  14 330-333
    PubMedGoogle Scholar
  • 5 Barchas J D, Freedman D X. Brain amines: Response to physiological stress.  Biochem Pharmacol. 1963;  12 1232-1235
    CrossrefPubMedGoogle Scholar
  • 6 Blomstrand E, Celsing F, Newsholme E A. Changes in plasma concentrations of aromatic and branced-chain amino acids during sustained exercise in man and their possible role in fatigue.  Acta Physiol Scand. 1988;  133 115-121
    PubMedGoogle Scholar
  • 7 Blomstrand E, Hassmen P, Ekblom B, Newsholme E A. Administration of branched-chain amino acids during sustained exercise -effects on performance and on plasma concentrations of some amino acids.  Eur J Appl Physiol . 1991;  63 83-88
    CrossrefPubMedGoogle Scholar
  • 8 Borg G. The reliability and validity of a physical work test.  Acta Physiol Scand . 1962;  55 33-36
    PubMedGoogle Scholar
  • 9 Bowsher D J, Rower H M, Lemberger L. Pressor response to tyramine and norepinephrine after subchronic administration of fluoxetine to man.  Life Sci. 1988;  2569 2575
    PubMedGoogle Scholar
  • 10 Carboni E, Di Chiara G. Serotonin release estimated by transcortical dialysis in freely moving rats.  Neurosci. 1989;  32 637-645
    CrossrefPubMedGoogle Scholar
  • 11 Carlsson L A, Lindqvist M. Effects of antidepressant agents on the synthesis of brain monoamines.  J Neural Trans. 1978;  43 73-91
    PubMedGoogle Scholar
  • 12 Chaouloff F, Elghozi J L, Guezzenec Y, Laude D. Effects of conditioned running on plasma, liver and brain tryptophan and brain 5-hydroxytryptamine metabolism of the rat.  Br J Pharmacol . 1985;  86 33-41
    PubMedGoogle Scholar
  • 13 Chaouloff F, Laude D, Guezzenec Y, Elghozi J L. Motor activity increases tryptophan, 5-hydroxyindoleacetic acid, and homovanillic acid in ventricular cerebrospinal fluid of the conscious rat.  J Neurochem. 1985;  46 1313-1316
    PubMedGoogle Scholar
  • 14 Chaouloff F, Kennet G A, Serrurier B, Merino D, and Curzon G. Amino acid analysis demonstrates that increased plasma free tryptophan causes the increase of brain tryptophan during exercise in the rat.  J Neurochem. 1985;  46 1647-1650
    PubMedGoogle Scholar
  • 15 Chaouloff F. Serotonin1C,2 receptors and endurance performance. An Illustration of the limits of pharmacological tools in exercise science.  Int J Sports Med. 1994;  15 339
    PubMedGoogle Scholar
  • 16 Chaput Y, Blier P, de Montigny C. In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotonergic terminals.  J Neurosci. 1986;  6 2796-2801
    PubMedGoogle Scholar
  • 17 Cowen P J, Sargent P A. Changes in plasma prolactin during SSRI treatment: evidence for a delayed increase in 5-HT neurotransmission.  J Psychopharmacol. 1997;  11 345-348
    PubMedGoogle Scholar
  • 18 Curme H, Colmbus R, Dappen G, Eder T, Fellows W, Figueras J, Glover C, Hill D, Lawton W, Muka E. Multilayer film for clinical analysis: general concepts.  Cli Chem. 1978;  24 1335-1336
    PubMedGoogle Scholar
  • 19 Dailey J W, Yan Q S, Mishra P K, Burger R L, Jobe P C. Effects of fluoxetine on convulsions and on brain serotonin as detected by microdialysis in genetically epilepsy-prone rats.  J Pharmacol Exp Ther. 1992;  260 533-540
    PubMedGoogle Scholar
  • 20 Davis M, Bailey S, Jackson D. Effects of a serotonin agonist during prolonged exercise to fatigue in humans.  Med Sci Sports Exerc. 1993;  25 78
    PubMedGoogle Scholar
  • 21 Demacker P, Hijmans A, Jansen A. Enzymatic and chemical-extraction determinants of free fatty acids in serum compared.  Clin Chem. 1982;  28 1765-1766
    PubMedGoogle Scholar
  • 22 De Meirleir K L, L‘Hermite-Baleriaux M, L’Hermite M, Rost R, Hollmann W. Evidence for serotonergic control of exercise-induced prolactin secretion.  Horm Metab Res. 1985;  17 380-381
    PubMedGoogle Scholar
  • 23 Dinan T G. Serotonin and the regulation of the hypothalamic, pituitary-adrenal axis function.  Life Sci. 1996;  58 1683-1694
    CrossrefPubMedGoogle Scholar
  • 24 Dinan T G, Scott L V. The influence of cortisol on spontaneous and 5-HT stimulated prolactin release in man.  J Basic Clin Physiol Pharmacol. 1996;  7 45-56
    PubMedGoogle Scholar
  • 25 Eison A S, Yocca F D, Gianustos G. Noradrenergic denervation alters serotonin2-mediated behavior but not serotonin2 receptor number in rats: modulatory role of beta-adrenergic receptors.  J Pharmacol Exp Ther. 1988;  246 571-577
    PubMedGoogle Scholar
  • 26 Fernstrom J D, Wurtman R J. Brain serotonin content: physiological regulation by plasma neutral amino acids.  Science. 1972;  178 414-416
    CrossrefPubMedGoogle Scholar
  • 27 Fuller R W, Perry K W, Molloy B B. Effect of an uptake inhibitor on serotonin metabolism in rat brain: Studies with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Lilly 110 140).  Life Sci. 1974;  15 1161-1171
    PubMedGoogle Scholar
  • 28 Fuller R W. Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis.  Life Sci. 1994;  55 163-167
    CrossrefPubMedGoogle Scholar
  • 29 Fuller R W. Serotonin receptors involved in the regulation of pituitary-adrenocortical function in rats.  Behav Brain Res. 1996;  73 215-219
    PubMedGoogle Scholar
  • 30 Gerlo E, Malfait R. High-performance liquid chromatographic assay of free norepinephrine, epinephrine, dopamine, vanillylmandelic acid and homovanillic acid.  J Chromatogr. 1985;  343 9-20
    PubMedGoogle Scholar
  • 31 Guan X M, McBride W J. Fluoxetine increases the extracellular levels of serotonin in the nucleus accumbens.  Brain Res Bull. 1988;  21 43-46
    CrossrefPubMedGoogle Scholar
  • 32 Hickey M S, Costill D L, McConell G K, Widrick J J, Tanaka H. Day to day variation in time trial cycling performance.  Int J Sports Med. 1992;  13 467-470
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Jacobs B L, Fornal C A. 5-HT and motor control: a hypothesis.  Trends Neurosci. 1993;  16 346-352
    CrossrefPubMedGoogle Scholar
  • 34 Jeukendrup A, Saris W HM, Brouns F, Kester A DM. A new validated endurance performance test.  Med Sci Sports Exerc. 1996;  28 266-270
    CrossrefPubMedGoogle Scholar
  • 35 Laakman G, Schumacher G, Benkert O, von Weerder K. Stimulation of growth hormone secretion by desipramine and clorimipramine in man.  J Clin Endocr Metab. 1977;  44 1010-1013
    PubMedGoogle Scholar
  • 36 MacLean D A, Graham T E. Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans.  J Appl Physiol. 1993;  74 2711-2717
    PubMedGoogle Scholar
  • 37 Madras B K, Cohen E L, Messing R, Munro H N, Wurtman R J. Relevance of free tryptophan in serum to tissue tryptophan concentrations.  Metabolism. 1974;  23 1107-1116
    CrossrefPubMedGoogle Scholar
  • 38 Maj J, Rogoz Z, Skuza G, Wedzony K. The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non competitive NMDA receptor antagonist.  J Neural Transm. 1996;  103 131-146
    CrossrefPubMedGoogle Scholar
  • 39 Malgie I, Trillat A C, Jacquot C, Gardier A M. Effects of acute fluoxetine on extracellular serotonin levels in the raphe: an in vivo microdialysis study.  Eur J Pharmacol. 1995;  14 286 213-217
    PubMedGoogle Scholar
  • 40 Marvin G, Sharma A, Aston W, Field C, Kendall M J, Jones D A. The effects of buspirone on perceived exertion and time to fatigue in man.  Exp Physiol. 1997;  82 1057-1060
    PubMedGoogle Scholar
  • 41 Mclellan T M, Cheung S, Jacobs I. Variability of time to exhaustion during submaximal exercise.  Can J Appl Physiol. 1995;  20 39-51
    PubMedGoogle Scholar
  • 42 Meeusen R, De Meirleir K. Exercise and brain neurotransmission.  Sports Med. 1995;  20 160-188
    PubMedGoogle Scholar
  • 43 Meeusen R, Thorré K, Chaouloff F, Sarre S, De Meirleir K, Ebinger G, Michotte Y. Effects of tryptophan and/or acute running on extracellular 5-HT and 5-HIAA levels in the hippocampus of food deprived rats.  Brain Res. 1996;  740 245-252
    Google Scholar
  • 44 Meeusen R, Smolders I, Sarre S, De Meirleir K, Keizer H, Serneels M, Ebinger G, Michotte Y. Endurance training effects on neurotransmitter release in rat striatum: an in vivo microdialysis study.  Acta Physiol Scand. 1997;  159 335-341
    CrossrefPubMedGoogle Scholar
  • 45 Meeusen R, Roeykens J, Magnus L, Keizer H, De Meirleir K. Endurance performance in humans: the effect of a dopamine precursor or a specific serotonin (5-HT2A/2C) antagonist.  Int J Sports Med. 1997;  18 571-577
    PubMedGoogle Scholar
  • 46 Meltzer H Y, Nash J F. Serotonin and mood: neuroendocrine aspects. In: Ganten D, Pfaff D (eds) Current Topics in Neuroendocrinology. Vol 8.  Berlin; Springer 1988
    Google Scholar
  • 47 Newsholme E A, Acworth I, Blomstrand E. Amino acids, brain neurotransmitters and a functional link between muscle and brain that is important in sustained exercise. In: Benzi G. (ed) Advances in Myochemistry.  London; John Libby Eurotext 1987: 127-138
    Google Scholar
  • 48 Pannier J L, Bouckaert J J, Lefebvre R A. The antiserotonin agent pizotifen does not increase endurance performance in humans.  Eur J Appl Physiol. 1995;  72 175-178
    CrossrefPubMedGoogle Scholar
  • 49 Perry K W, Fuller R W. Effect of fluoxetine on serotonin and dopamine concentration in microdialysis fluid from rat striatum.  Life Sci. 1992;  50 1683-1690
    CrossrefPubMedGoogle Scholar
  • 50 Rigdon G C, Wang C M. Serotonin uptake blockers inhibit the firing of presumed serotonergic dorsal raphe neurons in vitro.  Drug Dev Res. 1991;  22 135-140
    CrossrefPubMedGoogle Scholar
  • 51 Rutter J J, Auerbach S B. Acute uptake inhibition increases extracellular serotonin in the rat forebrain.  J Pharmacol Exp Ther. 1993;  265 1319-1324
    PubMedGoogle Scholar
  • 52 Santiago M, Matarredona E R, Machado A, Cano J. Influence of serotonergic drugs on in vivo dopamine extracellular output in rat striatum.  J Neurosci Res. 1998;  52 591-598
    CrossrefPubMedGoogle Scholar
  • 53 Sills T L, Greenshaw A J, Baker G B, Fletcher P J. Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction.  Psychopharmacol. 1999;  141 421-427
    PubMedGoogle Scholar
  • 54 Struder H K, Hollman W, Platen P, Donike M, Gotzmann A, Weber K. Alterations in plasma free tryptophan and large neutral amino acids do not affect perceived exertion and prolactin during 90 min of treadmill exercise.  Int J Sports Med . 1996;  17 73-79
    PubMedGoogle Scholar
  • 55 Struder H K, Hollman W, Platen P, Duperly J, Fischer H G, Weber K. Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans.  Horm Metab Res . 1998;  30 188-194
    PubMedGoogle Scholar
  • 56 Tanda G, Frau R, Di Chiara G. Local 5-HT3 receptors mediate fluoxetine but not desipramine-induced increase of extracellular dopamine in the prefrontal cortex.  Psychopharmacol. 1995;  119 15-19
    PubMedGoogle Scholar
  • 57 Tuomisto J, Mannisto P. Neurotransmitter regulation of anterior hormones.  Pharmac Rev. 1985;  37 249-332
    PubMedGoogle Scholar
  • 58 Van de Kar L D. The neuroendocrine pharmacology of serotonergic (5-HT) neurons.  Ann Rev Pharmacol Toxic. 1991;  31 289-320
    PubMedGoogle Scholar
  • 59 Wilckens T, Schweiger U, Pirke K. Activation of 5-HT1C-receptors suppresses excessive wheel running induced by semi-starvation in the rat.  Psychopharmacol. 1992;  109 77-84
    PubMedGoogle Scholar
  • 60 Wilson W, Maughan R. Evidence for a possible role of 5-hydroxytryptamine in the genesis of fatigue in man: administration of paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise.  Exp Physiol. 1992;  77 921-924
    CrossrefPubMedGoogle Scholar
  • 61 Wong D T, Horng J S, Bymaster F P, Hauser K, Molloy B B. A new selective inhibitor of serotonin uptake: Lilly 110 140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine.  Life Sci. 1974;  15 471-479
    CrossrefPubMedGoogle Scholar
  • 62 Wong D T, Bymaster F P, Horng J S, Molloy B B. A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine.  J Pharmacol Exp Ther. 1975;  193 804-811
    PubMedGoogle Scholar

Prof. Dr. Romain Meeusen


Department of Human Physiology and Sportsmedicine
Free University Brussel

Pleinlaan 2
1050 Brussels
Belgium


Phone: Phone:+32 (2) 6292222

Fax: Fax:+32 (2) 6292876

Email: email:rmeeusen@vub.ac.be

      >