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Bell & Howell Information and Leaming 300 North Zeeb Road, Ann Arbor, MI 481064346 USA 800-521-0600 Effects of Modafd on Physiological and Perceptual Responses During Exercise Peter Dinich A thesis submittea in conformity with the requirements for the degree of Master of Science in the Exercise Sciences Programme Graduate Department of Commu~tyHealth, University of Toronto O Copyright by Peter Dinich, 1998 National Library Bibliothéque nationale du Canada Acquisitions and Acquisitions et Bibliographie Services senices bibliographiques 395 Wellington Street 395, me Wellington Ottawa ON K1A ON4 Ottawa ON KIA ON4 Canada canada The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfichellZh, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. Effects of Modafhil on Physiobgical and Perceptual Responses During Exercise Master of Science, 1998 Peter Dinich Graduate Department of Community Health University of Toronto Abstract Modafinil (M) belongs to a new class of dmgs which elicit "arousal" properties similar to amphetamines, but with less potent side-effects. One aim of this study was to corKim that acute treatment with M (4mg-kg-') would have an ergogenic effect on high intensity exercise performance. Eight males cycled to exhaustion at 85% VOz max after both M and placebo (P) treatments, using a double-blind experimental design. M prolonged time to exhaustion by 10-15%. The mechanism responsible for this effect is most likely related to a mechanisrn of action in the CNS that enhanced the level of arousal and vigilance. A second objective was to assess whether M would cause an overconfidence effect (i.e. a self- appraised overestimation of actual performance abilities) and enhanced cognitive performance. Seventeen subjects who participated in this experiment were randomly treated with M and P after familiarization trials. M did not cause an overconfidence effect, nor show any disturbance in self-monitoring ability. Moreover, M significantly shortened reaction time and consequently enhanced cognitive efficiency. In conclusion, M was well tolerated and had positive effects on physical and cognitive performance. To Vesna, Branko and Saslta with love Table of Contents Abstract ...................................................................................i List of Figures and Tables .............................................................v List of Abbreviations ...................................................................vi Chapter 1. Introduction .............................................................-1 Chapter 2. Literature Review ......................................................-4 2.1. Central Fatigue ......................................................... -4 2.1.1 Perception of Fatigue .......................................... 5 2.1.2 Role of Neurotransmitters in Exercise Fatigue ............ 8 2.1.3 Brain Catecholamines and CNS fatigue.................... 9 2.1 -4 Brain Serotonin and CNS fatigue ...........................-11 2.2. Modafïinil................................................................ 14 2.2.1 Pharrnacokinetic Profile of Modafiil ....................... 17 2.2.2 Dosage and Toxicity ........................................... 17 2.2.3 Mechanism of Action ...........................................18 2.2.4 Modafinil and Cognitive Performance ......................-23 2.2.5 Self-Monitoring of Cognitive Performance................ -27 2.2.6 Overconfidence effect ......................................... 29 Chapter 3 . Study Objectives and Hypotheses .................................. 32 3.1. Objectives ..............................................................-32 3.2 Hypotheses............................................................. -32 Chapter 4. Materials and Methods .................................................. 33 4.1. Subjects................................................................... 33 4.2. Experimental Protocol ...................................................34 4.2.1 Endurance Ride to Exhaustion ...................................34 4.2.2 Production Protocol Ride ........................................ 35 Measurements made during trials .....................................-38 Heart Rate .......................................................-38 Blood Pressure ...................................................38 Metabolic Gas Exchange..................................... -38 Rating of Perceived Exertion ..................................39 Line Cornparison Task and Overconfidence effect .........39 Blood Metabolite and Neurotransrnitter determinations... 40 Data Analyses ............................................................ 43 4.4.1 Analysis of Variance (ANOVA) .............................43 4.4.2 Power Analysis .................................................43 Chapter 5. Results .................................................................... -44 5.1 Endurance Ride to Exhaustion ...............................-44 5.2 Production Protocol Ride ......................................49 Chapter 6 . Discussion................................................................ 56 6.1. Review of Objectives and Hypotheses .............................. 56 6.2. Main Findings ..........................................................56 6.3. Overconfidence Effect ................................................ 58 6.4. Indicators of Cognitive Performance ................................60 6.5. Subjective effects and Individual variations ........................61 6.6. Compantive Studies ................................................... 62 iv Chapter 7 . Limitations ............................................................... 66 Conciusions.............................................................. 66 Recommendations for Future Study ................................. -67 Aclaiowledgements.................................................... -69 References .................................................................................. -70 Appendices A: Letter of Approval from the University of Toronto ............ 88 B : Approved Expenmental Protocol ................................. -89 C: Raw Data ............................................................102 List of Figures and Tables Figures Figure 2.1 . Chernical Structure of Modafïnil....................................... 15 Figure 4.la . Time Line for Experimental Protocol for ER ........................ 35 Figure 4- 1b . Time Line for Experirnental Protocol for PPR .......................35 Figure Time to Exhaustion during Exercise at 85% VOz max .............44 Figure Effect of Order of Trial During ER .................................... 45 Figure Heart Rate during ER ................................................... 45 Figure VOz, VE and RQ during ER ............................................ 46 Figure RPE during ER ........................................................... 47 Figure Plasma Lactate during ER .............................................. 47 Figure Plasma Glucose and FFA during ER ................................ -48 Figure Average Watts at Various RPE ....................................... 50 Figure Actual Exercise Time in Watts selected.............................. 51 Figure 5-10 . Reaction Time during Line Cornparison Task ...................... 53 Figure 5-1 1 . Plasma Serotonin during ER and PPR ...............................54 Figure 5-12 . Changes in E. NE. and DA during ER ..............................55