dopamine activity would lead to a reduction in
motivation, arousal and/or motor control that
would contribute to CNS fatigue.
It is clear that drug-induced increases in
dopamine activity as well as electrical brain stim-
ulation of the primary dopamine system in the
brain can motivate various exercise tasks in rats
and can delay fatigue during treadmill running.
For example, pretreatment of rats with amp-
hetamine, a dopamine releaser with powerful
rewarding properties, or apomorphine, a
dopamine agonist, has been shown to delay
fatigue (Gerald 1978; Heyes et al.1988). There are
also numerous reports of amphetamine use to
control fatigue and improve performance in ath-
letes and soldiers (Ivy 1983). Electrical stimula-
tion of the VTA or other areas of the mesolimbic
dopamine pathway mediate reinforcement and
reward (Olds & Fobes 1981). It has recently been
shown to motivate rats to lift weights (Garner et
al.1991), run on a motorized treadmill (Burgess
et al. 1991) and run in running wheels
(Schwarzberg & Roth 1989). We did a series of
studies in which activation of this dopaminergic
reward system was used to motivate rats to run
on a treadmill (Burgess et al.1991, 1993a, 1993b).
In one of the studies we compared run time to
fatigue on a motorized treadmill in rats that ran
for rewarding VTA stimulation vs. those in
which the fear of an electric shock grid placed
at the back of the treadmill was used as motiva-
tion. We found that rats ran significantly longer
(25 m · min–1, 5% grade) while receiving VTA
stimulation (63±10 min) that when they received
the electric shocks (42±10 min). We did not
measure neurotransmitters in this study to
confirm a presumed role of elevated dopamine in
delayed fatigue in this experiment, but in other
experiments it was determined that this delay in
fatigue was not likely related to cardiovascular
or metabolic function.
There is also good evidence that increased
dopamine metabolism occurs normally during
exercise. Regional brain analysis shows that
dopamine metabolism is enhanced during tread-
mill exercise in the midbrain, hippocampus,
striatum and hypothalamus (Chaouloff et al.
178 nutrition and exercise
1987; Bailey et al.1993a). Increased dopamine
metabolism has been shown to be a good marker
for speed, direction and posture of moving
animals (Freed & Yamamoto 1985). Conversely,
endurance performance was impaired following
destruction of dopaminergic neurones by 6-
hydroxydopamine, an effect diminished by
giving back a drug that increases dopamine
activity (i.e. apomorphine; Heyes et al.1988).
Baileyet al.(1993a) demonstrated a relation-
ship between decreased brain dopamine
metabolism and fatigue during prolonged tread-
mill running in rats. Fatigue was associated
with specific decreases in dopamine in the brain
stem and midbrain. These data, along with other
data showing a phasic inhibitory control of 5-HT
over dopamine-dependent forms of behaviour
(Soubrieet al.1984), led to the hypothesis that
elevated 5-HT, also associated with fatigue, may
inhibit dopamine activity (Davis & Bailey 1997).
Further support for this comes from studies that
show an inverse relationship between brain 5-
HT and dopamine in association with fatigue fol-
lowing administration of drugs that affect brain
5-HT and dopamine systems. When a 5-HT
agonist (quipizine dimalate) was administered to
rats prior to treadmill running, it appeared to
block the increase in dopamine at 1 h and fatigue
occurred early. Alternatively, a 5-HT antagonist
(LY53857) partially blocked the decrease in
dopamine and fatigue was delayed. Also, when
amphetamine is given to rats in doses known
to delay fatigue, brain 5-HT metabolism is
decreased (Chaouloff et al.1987). These data add
support to our hypothesis that central fatigue
occurs when dopamine is reduced in association
with elevated 5-HT (Davis & Bailey 1997).Nutrition, brain catecholamines
and CNS fatigue
Tyrosine is a non-essential, large, neutral, amino
acid found in dietary proteins and is the pre-
cursor of the neurotransmitters noradrenaline
and dopamine. Researchers, especially those
employed by the US Army, have been interested
in the possibility that tyrosine supplementation