Int J Sports Med 2001; 22(5): 317-322
DOI: 10.1055/s-2001-15645
Physiology and Biochemistry

© Georg Thieme Verlag Stuttgart · New York

Evidence that the Branched-Chain Amino Acid L-Valine Prevents Exercise-Induced Release of 5-HT in Rat Hippocampus

D. Gomez-Merino, F. Béquet, M. Berthelot, S. Riverain, M. Chennaoui, C. Y. Guezennec.
  • Department of Physiology: IMASSA-CERMA, Bretigny Sur Orge, France
Further Information

Publication History

Publication Date:
31 December 2001 (online)

The branched-chain amino acid L-valine competes with tryptophan for transport into the brain and has previously been shown to decrease brain 5-HT synthesis. The purpose of this study was to assess, using a combined venous catheterization and in vivo microdialysis method, the effect of pre-exercise L-valine administration on 5-hydroxytryptamine (5-HT) metabolism in the ventral hippocampus of rats submitted to an acute intensive treadmill running (120 min at 25 m × min-1 followed by 150 min of recovery). The presented results include measurement of extracellular tryptophan (TRP), the 5-HT precursor, and extracellular 5-hydroxyindoleacetic acid (5-HIAA), the 5-HT metabolite. The data clearly demonstrate that exercise induces 5-HT release in the rat hippocampus: in control group, hippocampal 5-HT levels increase from 123.7 ± 6.4 % at the end of exercise to 133.9 ± 6.4 % after 60 min of recovery. Moreover, two hours of intensive running induced significant increases both in extracellular TRP levels (from 120 min of exercise to 30 min of recovery) and 5-HIAA levels (from 90 min of exercise to 90 min of recovery). Pre-exercise administration of L-valine prevents significantly the exercise-induced 5-HT release: 5-HT levels are maintained to baseline during exercise and recovery. With regard to the competitive effect of L-valine with TRP, we could observe a treatment-induced decrease in brain TRP levels (from 120 min of exercise to the end of recovery). Besides, L-valine does not prevent exercise-induced increase in 5-HIAA levels. The present study evidences that an acute intensive exercise stimulates 5-HT metabolism in the rat hippocampus, and that a pre-exercise administration of L-valine prevents, via a limiting effect on 5-HT synthesis, exercise-induced 5-HT release. This study provides some anwers to previous human and animal investigations, showing physiological and psychological benefits of branched-chain amino acids supplementation on performance.


  • 1 Ahlborg G, Felig P, Hagenfeldt L, Hendler R, Wahren J. Substrate turnover during prolonged exercise in man: splanchnic and leg metabolism of glucose, free fatty acids and amino acids.  J Clin Invest. 1974;  53 1080-1090
  • 2 Bigard A X, Lavier P, Ulmann L, Douce P, Guezennec C Y. Branched-chain amino acid supplementation during repeated prolonged skiing exercises at altitude.  Int J Sports Nutr. 1996;  6 295-306
  • 3 Bailey S P, Davis J M, Ahlborn E N. Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue.  J Appl Physiol. 1993;  74 3006-3012
  • 4 Bigland-Ritchie B, Furbush F, Woods J J. Fatigue of intermittent submaximal voluntary contractions: central and peripheral factors.  J Appl Physiol. 1986;  61 421-429
  • 5 Blomstrand E, Perrett D, Parry-Billings M, Newsholme E A. Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytryptamine metabolism in six different brain regions in the rat.  Acta Physiol Scand. 1989;  136 473-481
  • 6 Blomstrand E, Hassmen P, Ekblom B, Newsholme E A. Administration of branched-chain amino acids during sustained exercise: effect on performance and on plasma concentration of some amino acids.  Eur J Appl Physiol. 1991;  63 83-88
  • 7 Blomstrand E, Hassmen P and EA N ewsholme. Effect of branched-chain amino acid supplementation on mental performance.  Acta Physiol Scand. 1991;  143 225-226
  • 8 Blomstrand E, Hassmen P, Ekblom B, Newsholme E A. Influence of ingesting a solution of branched-chain amino acids on perceived exertion during exercise.  Acta Physiol Scand. 1997;  159 41-49
  • 9 Calders P, Pannier J L, Matthys D M, Lacroix E M. Pre-exercise branched-chain amino acid administration increases performance in rats.  Med Sci Sports Exerc. 1997;  29 1182-1186
  • 10 Calders P, Matthys D, Derave W, Pannier J L. Effect of branched-chain amino acids (BCAA), glucose, and glucose plus BCAA on endurance performance in rats.  Med Sci Sports Exerc. 1999;  31 583-587
  • 11 Chaouloff F, Elghozi J L, Guezennec C Y, Laude D. Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-HT metabolism of the rat.  Br J Pharmacol. 1985;  86 33-41
  • 12 Chaouloff F , Kennett G A, Serrurrier B, Mérino D, Curzon G. Amino acid analysis demonstrates that increased plasma free tryptophan causes the increase of brain tryptophan during exercise in the rat.  J Neurochem. 1986;  46 1647-1650
  • 13 Davis J M. Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis.  Int J Sport Nutr. 1995;  5 S29-S38
  • 14 Davis J M, Welsh R S, De Volve K L, Alderson N A. Effects of branched-chain amino acids and carbohydrate on fatigue during intermittent, high-intensity running.  Int J Sports Med. 1999;  20 309-314
  • 15 Early R J. Capillary gas chromatographic analysis of amino acids in blood and protein hydrolysates as tert-butyldimethylsilyl derivatives.  J Chromato. 1987;  416 15-23
  • 16 Gandevia S J, Allen G M, Butter J E, Taylor J L. Supraspinal factor in human muscle fatigue. Evidence for subspinal output from the motor cortex.  J Physiol. 1996;  490 529-536
  • 17 Gartside S E, Cowen P J, Sharp T. Evidence that the large amino acid L-valine decreases electrically-evoked release of 5-HT in rat hippocampus in vivo.  Psychopharmacol. 1992;  109 251-253
  • 18 Guezennec C Y, Abdelmaki A, Serrurier B, Merino D, Bigard X, Berthelot M, Pierard C, Peres M. Effects of prolonged exercise on brain ammonia and amino acids.  Int J Sports Med. 1998;  19 323-327
  • 19 Hjorth S and Tao R. The putative 5-HT1B receptor agonist CP-93,129 suppresses rat hippocampal 5-HT release in vivo: comparison with RU 24 969.  Eur J. Pharmacol;  209 249-252
  • 20 Kalén P, Strecker R E, Rosengren E, Björklund A. Endogenous release of neuronal serotonin and 5-hydroxyindolacetic acid in the caudate putamen of the rat as revealed by intracerebral dialysis coupled to high-performance liquid chromatography with fluorometric detection.  J Neurochem. 1988;  51 1422-1435
  • 21 Knapik J, Meredith C, Jones B, Fielding R, Young V, Evans W. Leucine metabolism during fasting and exercise.  J Appl Physiol. 1991;  70 43-47
  • 22 Kreiss D S, Weiland S, Lucki I. The presence of a serotonin uptake inhibitor alters pharmacological manipulations of serotonin release.  Neuroscience. 1993;  52 295-301
  • 23 Maura G, Bonanno G, Raiteri M. Presynaptic alpha 2-adrenoreceptors mediating inhibition of noradrenaline and 5-hydroxytryptamine release in rat cerebral cortex: Further characterization as different alpha 2-adrenoreceptor subtypes.  Naunyn-Schmiedebergs Arch Pharmacol. 1992;  345 410-416
  • 24 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
  • 25 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. (ed) Advances in Biochemistry. London; John Libbey Eurotext Ltd 1987: 127-133
  • 26 Nicolaidis S, Rowland N, Meile M J, Marfaing-Jallat P, Pesez A. A flexible technique for long-terme infusions in unrestrained rats.  Pharmacol Behav. 1974;  2 131-136
  • 27 Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates, . New York; Academic Press 1982
  • 28 Schlicker E, Classen K, Göthert M. GABAB receptor-mediated inhibition of serotonin release in the rat brain.  Naunyn-Schmiedeberg’s Arch Pharmacol. 1984;  326 99-105
  • 29 Sharp T, Bramwell S R, Clark D, Grahame-Smith D G. In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity.  J Neurochem. 1989;  53 234-240
  • 30 Sharp T, Bramwell S R, Grahame-Smith D G. Effect of acute administration of L-tryptophan on the release of 5-HT in rat hippocampus in relation to serotoninergic neuronal activity: an in vivo microdialysis study.  Life Sci. 1992;  50 1215-1223
  • 31 Torigoe K, Potter P E, Katz D. Branched-chain amino acid-induced hippocampal norepinephrine release is antagonized by picrotoxin: evidence for a central mode of action.  Brain Res Bull. 1999;  49 281-284
  • 32 Verger P H, Aymard P, Cynobert L, Anton G, Luigi R. Effects of administration of branched-chain amino acids vs. glucose during acute exercise in the rat.  Physiol Behav. 1994;  55 523-526

Danielle Gomez-Merino 


91223 Brétigny-sur-Orge Cedex

Phone: Phone:+31(69)883300 extension: 73746

Fax: Fax:+31(69)883302