Amphetamine and α-methyl-p-tyrosine affect the exercise-induced imbalance between the availability of tryptophan and synthesis of serotonin in the brain of the rat

Chaouloff, Francis; Laude, Dominique; Merino, D.; Serrurrier, Bernard; Guezennec, Y.; Elghozi, Jean‐Luc

doi:10.1016/0028-3908(87)90254-1

Cited by 79 publications

(36 citation statements)

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“…Thus the a-v difference of dopamine across the brain was not changed in response to exercise, and the elevated arterial and jugular venous dopamine concentrations at the end of the hyperthermic exercise trial were not related to accelerated cerebral dopamine release or increased tyrosine uptake. Dopaminergic neurons are considered to be important for motor activation (22), but exercise may only affect the dopamine level in small regions of the brain (10,40). Furthermore, exercise may elevate the global dopamine level in the brain without affecting the cerebral release via the jugular venous blood, because polar catecholamines do not readily penetrate the blood-brain barrier (2,26), and maybe only dopamine released into the hypophysial portal blood will appear in the jugular blood (23).…”

Section: Discussionmentioning

confidence: 99%

“…Some support for the involvement of serotonin in fatigue is obtained from studies that have attempted to alter the cerebral serotonin level by means of nutritional and pharmacological manipulations (41), but the results are ambiguous (6,8,13,14). Influence of other neurotransmitters on fatigue has also been proposed, and dopamine is considered for its involvement in the initiation and control of movement (10,22). Studies on rats and cats indicate that regional cerebral dopamine synthesis and metabolism are enhanced during exercise (see Ref.…”

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confidence: 99%

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Neurohumoral responses during prolonged exercise in humans

Nybo¹,

Nielsen²,

Blomstrand³

et al. 2003

Journal of Applied Physiology

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.-This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O 2/CHO ϭ arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 Ϯ 0.1°C (mean Ϯ SE) in the control trial, whereas it increased to 39.7 Ϯ 0.2°C in the hyperthermic trial, with a concomitant increase in perceived exertion (P Ͻ 0.05). At rest, the brain had a small release of tryptophan (arteriovenous difference of Ϫ1.2 Ϯ 0.3 mol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 Ϯ 0.3 (P Ͻ 0.05), whereas it returned to the baseline level of ϳ6 within 5 min after the control trial. The lowering of O2/CHO was established by an increased arteriovenous glucose difference (1.1 Ϯ 0.1 mmol/l during recovery from hyperthermia vs. 0.7 Ϯ 0.1 mmol/l in control; P Ͻ 0.05). The present findings indicate that the brain has an increased need for carbohydrates during recovery from strenuous exercise, whereas enhanced perception of effort as observed during exercise with hyperthermia was not related to alterations in the cerebral balances of dopamine or tryptophan.brain; dopamine; hyperthermia; tryptophan ALTHOUGH FATIGUE MAY RELATE to both peripheral (muscular) and central factors (4, 31, 52), attention has primarily been on the association to muscular factors. Hypotheses have connected central fatigue with alterations in the cerebral level of different neurotransmitters, but the cerebral balances of these neurotransmitters, their precursors, or metabolites have actually never been determined during prolonged exercise in humans. Central fatigue is aggravated by hyperthermia (47, 48), but the neurobiological mechanism(s) underlying this type of fatigue is unknown. Special attention has been given to the synthesis and metabolism of serotonin (5-hydroxytryptamine), because of its role in arousal, sleepiness, and mood (5, 13, 15, 42, 51). Cerebral serotonin kinetics cannot be assessed directly in humans, because its passage across the blood-brain barrier is limited (27). However, determination of the cerebral uptake of tryptophan (TRP), the precursor for the synthesis of serotonin, may provide an indication of changes in the serotonin level within the brain, because transport of TRP into the brain is the ratelimiting step in the synthesis of serotonin (5, 20). Some support for the involvement of serotonin in fatigue is obtained from studies that have attempted to alter the cerebral serotonin level by me...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neurohumoral responses during prolonged exercise in humans

Nybo¹,

Nielsen²,

Blomstrand³

et al. 2003

Journal of Applied Physiology

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“…5, which shows that in the two CHO groups that have less FFA there is a reduction in free tryptophan. Previous research suggests that fatigue after prolonged exercise is associated with elevations of free tryptophan and serotonin in various regions of the brain and cerebrospinal fluid (6,(8)(9)(10) resulting from high concentrations of plasma free tryptophan. It is possible that, in the present study, the feeding of glucose resulted in a reduction of free tryptophan and a concomitant reduction of the tryptophan and serotonin in the brain and an improvement in performance.…”

Section: Discussionmentioning

confidence: 99%

“…Brain serotonin synthesis depends on the availability of free tryptophan, its amino acid precursor, and the activity of the rate-limiting enzyme, tryptophan hydroxylase (7,10). Similarly, tyrosine is the amino acid precursor to dopamine (32).…”

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confidence: 99%

“…Struder et al (30) reported no beneficial effect of tyrosine supplementation when subjects cycled to exhaustion. On the other hand, Chaouloff et al (10) reported that high doses of ␣-methyl-p-tyrosine improved exercise performance in rats, and the improved performance correlated with elevated dopamine concentration in the brain. Some investigations have shown that tyrosine administration increases dopamine synthesis and concentration in the brain (1,19,20), whereas others have shown that tyrosine administration leads to improvement of mood and well-being in human subjects under stress (5,24).…”

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Effects of l-tyrosine and carbohydrate ingestion on endurance exercise performance

Chinevere

Sawyer

Creer

et al. 2002

Journal of Applied Physiology

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To test the effects of tyrosine ingestion with or without carbohydrate supplementation on endurance performance, nine competitive cyclists cycled at 70% peak oxygen uptake for 90 min under four different feeding conditions followed immediately by a time trial. At 30-min intervals, beginning 60 min before exercise, each subject consumed either 5 ml/kg body wt of water sweetened with aspartame [placebo (Pla)], polydextrose (70 g/l) (CHO), L-tyrosine (25 mg/kg body wt) (Tyr), or polydextrose (70 g/l) and L-tyrosine (25 mg/kg body wt) (CHOϩTyr). The experimental trials were given in random order and were carried out by using a counterbalanced double-blind design. No differences were found between treatments for oxygen uptake, heart rate, or rating of perceived exertion at any time during the 90-min ride. Plasma tyrosine rose significantly from 60 min before exercise to test termination (TT) in Tyr (means Ϯ SE) (480 Ϯ 26 mol) and CHOϩTyr (463 Ϯ 34 mol) and was significantly higher in these groups from 30 min before exercise to TT vs. CHO (90 Ϯ 3 mol) and Pla (111 Ϯ 7 mol) (P Ͻ 0.05). Plasma free tryptophan was higher after 90 min of exercise, 15 min into the endurance time trial, and at TT in Tyr (10.1 Ϯ 0.9, 10.4 Ϯ 0.8, and 12.0 Ϯ 0.9 mol, respectively) and Pla (9.7 Ϯ 0.5, 10.0 Ϯ 0.3, and 11.7 Ϯ 0.5 mol, respectively) vs. CHO (7.8 Ϯ 0.5, 8.6 Ϯ 0.5, and 9.3 Ϯ 0.6 mol, respectively) and CHOϩTyr (7.8 Ϯ 0.5, 8.5 Ϯ 0.5, 9.4 Ϯ 0.5 mol, respectively) (P Ͻ 0.05). The plasma tyrosine-to-free tryptophan ratio was significantly higher in Tyr and CHOϩTyr vs. CHO and Pla from 30 min before exercise to TT (P Ͻ 0.05). CHO (27.1 Ϯ 0.9 min) and CHOϩTyr (26.1 Ϯ 1.1 min) treatments resulted in a reduced time to complete the endurance time trial compared with Pla (34.4 Ϯ 2.9 min) and Tyr (32.6 Ϯ 3.0 min) (P Ͻ 0.05). These findings demonstrate that tyrosine ingestion did not enhance performance during a cycling time trial after 90 min of steady-state exercise. central fatigue; cycling; perceived exertion RECENTLY, IT HAS BEEN HYPOTHESIZED that, during prolonged exercise, an increased concentration of brain serotonin may be an important factor in the onset of central nervous system fatigue (2-4, 8, 10, 27) and a high serotonin-to-dopamine ratio results in fatigue (17). Brain serotonin synthesis depends on the availability of free tryptophan, its amino acid precursor, and the activity of the rate-limiting enzyme, tryptophan hydroxylase (7, 10). Similarly, tyrosine is the amino acid precursor to dopamine (32). These amino acid precursors compete for transport across the bloodbrain barrier via the same carrier mechanism (17).We speculated that, if tyrosine were elevated in the blood by ingestion during exercise and competed for transport across the blood brain barrier with tryptophan, increased uptake of tyrosine and a decreased uptake of tryptophan could result in a lower brain serotonin/dopamine ratio and improved endurance.Limited research has been done on the effects of tyrosine ingestion on exercise endurance. Struder et al. (30) rep...

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Nutrition, Neurotransmitters and Central Nervous System Fatigue

Davis¹

2000

Nutrition in Sport

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Amphetamine and α-methyl-p-tyrosine affect the exercise-induced imbalance between the availability of tryptophan and synthesis of serotonin in the brain of the rat

Cited by 79 publications

References 24 publications

Neurohumoral responses during prolonged exercise in humans

Neurohumoral responses during prolonged exercise in humans

Effects of l-tyrosine and carbohydrate ingestion on endurance exercise performance

Nutrition, Neurotransmitters and Central Nervous System Fatigue

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