Performance and thermoregulatory effects of chronic bupropion administration in the heat

  • Bart Roelands
  • Hiroshi Hasegawa
  • Philip Watson
  • Maria Francesca Piacentini
  • Luk Buyse
  • Guy De Schutter
  • Romain MeeusenEmail author
Original Article


The combination of acute dopamine/noradrenaline reuptake inhibition (bupropion; BUP) and heat stress (30°C) significantly improves performance (9%). Furthermore the maintenance of a higher power output resulted in the attainment of significantly higher heart rates and rectal temperatures—above 40°C—in the BUP trial compared to the placebo trial. Since BUP is an aid to cease smoking that is taken for longer periods, question remains if similar performance and thermoregulatory effects are found following administration of BUP over several days (10 days). The purpose of the present study was to examine the effects of chronic BUP on exercise performance, thermoregulation and hormonal variables in the heat. Eight trained male cyclists participated in the study. Subjects completed two trials consisting of 60 min fixed intensity exercise (55% W max) followed by a time trial (TT) in a double-blind randomized crossover design. Exercise was performed in 30°C. Subjects took either placebo (PLAC) or BUP (Zyban™) for 3 days (150 mg), followed by 300 mg for 7 days. Chronic BUP did not influence TT performance (BUP 40′42″ ± 4′18″; PLAC 41′36″ ± 5′12″), but significantly increased core temperature (P = 0.030). BUP significantly increased circulating growth hormone levels (PLAC: 9.8 ± 5.8 ng L−1; BUP: 13 ± 6.8 ng L−1; P < 0.008). Discussion/conclusion: Chronic BUP did not influence TT performance in 30°C and subjects did not reach core temperature values as high as observed during the acute BUP study. It seems that chronic administration results in an adaptation of central neurotransmitter homeostasis, resulting in a different response to the drug.


Dopamine/noradrenaline reuptake inhibition Exercise Thermoregulation Central fatigue 



This study was supported by research funding from the Vrije Universiteit Brussel (OZR 607, 990, 1236). Further we want to acknowledge the assistance of Prof. Dr. Ilse Smolders for the preparation of the treatments.


  1. Borg GA (1982) Psychophysical bases of perceived exertion. Med Sci Sports Exerc 14:377–381PubMedGoogle Scholar
  2. Burgess ML, Davis JM, Borg TK, Buggy J (1991) Intracranial self-stimulation motivates treadmill running in rats. J Appl Physiol 71(4):1593–1597PubMedGoogle Scholar
  3. Chekeley SE (1980) Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychol Med 10:35–53CrossRefGoogle Scholar
  4. Committee for Proprietary Medicinal Products (2002) Bupropion hydrochloride, international non-proprietary name (INN): Bupropion. Euopean Agency for the Evaluation of Medicinal Products; CPMP/27610/02Google Scholar
  5. George T, O’Malley S (2004) Current pharmacological treatments for nicotine dependence. Trends Pharmacol Sci 25:42–48. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  6. Hasegawa H, Meeusen R, Sarre S, Diltoer M, Piacentini MF, Michotte Y (2005) Acute dopamine/noradrenaline reuptake inhibition increases brain and core temperature in rats. J Appl Physiol 99(4):1397–1401. doi: 10.1152/japplphysiol.00435.2005 PubMedCrossRefGoogle Scholar
  7. Hasegawa H, Piacentini MF, Sarre S, Michotte Y, Ishiwata T, Meeusen R (2008) Influence of brain catecholamines on the development of fatigue in exercising rats in the heat. J Physiol 586(1):141–149. doi: 10.1113/jphysiol.2007.142190 PubMedCrossRefGoogle Scholar
  8. Holm KJ, Spencer CM (2000) Bupropion: a review of its use in the management of smoking cessation. Drugs 59:1007–1024. doi: 10.2165/00003495-200059040-00019 PubMedCrossRefGoogle Scholar
  9. Jefferson JW, Pradko JF, Muir KT (2005) Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations. Clin Ther 27(11):1685–1695. doi: 10.1016/j.clinthera.2005.11.011 PubMedCrossRefGoogle Scholar
  10. Jeukendrup A, Saris WH, Brouns F, Kester AD (1996) A new validated endurance performance test. Med Sci Sports Exerc 28:266–270. doi: 10.1097/00005768-199602000-00017 PubMedGoogle Scholar
  11. Learned-Coughlin SM, Bergström M, Savitcheva I, Ascher J, Schmidt VD, Langstrom B (2003) In vivo activity of bupropion at the human dopamine transporter as measured by possitron emission tomography. Biol Psychiatry 54:800–805. doi: 10.1016/S0006-3223(02)01834-6 PubMedCrossRefGoogle Scholar
  12. Liu YL, Connoley IP, Harrison J, Heal DJ, Stock MJ (2002) Comparison of the thermogenic and hypophagic effects of sibutramine’s metabolite 2 and other monoamine reuptake inhibitors. Eur J Pharmacol 452:49–56. doi: 10.1016/S0014-2999(02)02226-4 PubMedCrossRefGoogle Scholar
  13. Meeusen R, Watson P, Hasegawa H, Roelands B, Piacentini MF (2006) Central Fatigue: the serotonine hypothesis and beyond. Sports Med 36(10):881–909. doi: 10.2165/00007256-200636100-00006 PubMedCrossRefGoogle Scholar
  14. Modell JG, Boyce S, Taylor E, Katholi C (2002) Treatment of atopic dermatitis and psoriasis vulgaris with bupropion SR: A pilot study. Psychosom Med 64:835–840. doi: 10.1097/01.PSY.0000021954.59258.9B PubMedCrossRefGoogle Scholar
  15. Nestler EJ, Hyman SE, Malenka RC (2001) Molecular neuropharmacology: a foundation for clinical neuroscience. McGraw-Hill, New YorkGoogle Scholar
  16. Paterson NE, Balfour DJ, Markou A (2007) Chronic bupropion attenuated the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell. Eur J Neurosci 25(10):3099–3108. doi: 10.1111/j.1460-9568.2007.05546.x PubMedCrossRefGoogle Scholar
  17. Piacentini MF, Meeusen R, Buyse L, De Schutter G, Kempenaers F, Van Nijvel J, De Meirleir K (2002) No effect of a noradrenergic reuptake inhibitor on performance in trained cyclists. Med Sci Sports Exerc 34(7):1189–1193. doi: 10.1097/00005768-200207000-00021 PubMedCrossRefGoogle Scholar
  18. Piacentini MF, Clinckers R, Meeusen R, Sarre S, Ebinger G, Michotte Y (2003) Effect of bupropion on hippocampal neurotransmitters and on peripheral hormonal concentrations in the rat. J Appl Physiol 95(2):652–656PubMedGoogle Scholar
  19. Piacentini MF, Meeusen R, Buyse L, De Schutter G, De Meirleir K (2004) Hormonal responses during prolonged exercise are influenced by a selective DA/NA reuptake inhibitor. Br J Sports Med 38:129–133. doi: 10.1136/bjsm.2002.000760 PubMedCrossRefGoogle Scholar
  20. Ramanathan LM (1964) A new weighting system for mean surface temperature of the human body. J Appl Physiol 19:531–532PubMedGoogle Scholar
  21. Roelands B, Hasegawa H, Watson P, Buyse L, De Schutter G, Piacentini MF, Meeusen R (2008a) Acute DA reuptake inhibition enhances performance in warm but not temperate conditions. Med Sci Sports Exerc 40(5):858–879. doi: 10.1249/MSS.0b013e3181659c4d Google Scholar
  22. Roelands B, Goekint M, Heyman E, Piacentini MF, Watson P, Hasegawa H, Buyse L, Pauwels F, De Schutter G, Meeusen R (2008b) Acute noradrenaline reuptake inhibition decreases performance in normal and high ambient temperature. J Appl Physiol 105:206–212. doi: 10.1152/japplphysiol.90509.2008 PubMedCrossRefGoogle Scholar
  23. Tella SR, Ladenheim B, Cadet JL (1997) Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine. J Pharmacol Exp Ther 281(1):508–513PubMedGoogle Scholar
  24. Watson P, Hasegawa H, Roelands B, Piacentini MF, Loovrie R, Meeusen R (2005) Acute dopamine/noradrenaline reuptake inhibition enhances human exercise performance in warm, but not temperate conditions. J Physiol 565(3):873–883. doi: 10.1113/jphysiol.2004.079202 PubMedCrossRefGoogle Scholar
  25. Yoshimura R, Yanagihara N, Hara K, Nakamura J, Toyohira Y, Ueno S, Izumi F (2001) Dual phases of functional change in norepinephrine transporter in cultured bovine adrenal medullary cells by long-term treatment with clozapine. J Neurochem 77:1018–1026. doi: 10.1046/j.1471-4159.2001.00316.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Bart Roelands
    • 1
  • Hiroshi Hasegawa
    • 1
    • 4
  • Philip Watson
    • 2
  • Maria Francesca Piacentini
    • 1
    • 3
  • Luk Buyse
    • 1
  • Guy De Schutter
    • 1
  • Romain Meeusen
    • 1
    Email author
  1. 1.Department of Human Physiology and Sports Medicine, Faculty of Physical Education and PhysiotherapyVrije Universiteit BrusselBrusselsBelgium
  2. 2.School of Sport and Exercise SciencesLoughborough UniversityLeicestershireUK
  3. 3.Department of Human Movement and Sport SciencesIstituto Universitario di Scienze Motorie (IUSM)RomeItaly
  4. 4.Laboratory of Exercise Physiology, Faculty of Integrated Arts and SciencesHiroshima UniversityHigashihiroshimaJapan

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