subjects drank 5 ml · kg–l·h–1of either a water
placebo, a 6% CHO drink or a 12% CHO drink
during prolonged cycling at 70% V
.
o2max.to
fatigue (Davis et al. 1992). When subjects
consumed the water placebo, plasma f-TRP
increased dramatically (in direct proportion to
plasma FFAs), while total TRP and BCAA
changed very little during the ride. When sub-
jects consumed either the 6% or 12% CHO solu-
tion, the increases in plasma f-TRP were greatly
reduced and fatigue was delayed by approxi-
mately 1 h. The CHO feedings caused a slight
reduction in plasma BCAA (19% and 31% in the
6% and 12% CHO groups, respectively), but this
decrease was probably inconsequential with
respect to the very large attenuation (five- to
sevenfold) of plasma f-TRP. Although it was not
possible to distinguish between the beneficial
effects of CHO feedings on central vs. peripheral
mechanisms of fatigue in this study, it was inter-
esting that the substantial delay in fatigue could
not be explained by typical markers of peripheral
muscle fatigue involving cardiovascular, ther-
moregulatory and metabolic function.
Brain catecholamines and CNS fatigue
The primary catecholamine neurotransmitters in
the brain are dopamine and noradrenaline. Both
neurotransmitters are formed from the amino
acid tyrosine in similar metabolic pathways, but
they are released from different neurones found
in different regions of the brain. The rate-limiting
step in their biosynthesis is the hydroxylation of
tyrosine to dihydroxyphenylalanine (l-dopa)
by the enzyme tyrosine hydroxylase. l-Dopa is
then decarboxylated to dopamine. In noradre-
naline neurones, dopamine is then converted
to noradrenaline by the enzyme dopamine b-
hydroxylase.
Dopamine and noradrenaline neurones modu-
late a wide variety of functions in the CNS.
Dopaminergic neurones arise primarily from cell
bodies in the ventral tegmental area (VTA) and
pars compacta of the substantia nigra (CSN). The
VTA gives rise to neurones of the mesolimbic and
mesocortical pathways that project to many com-
ponents of the limbic system. These neurones are
involved in various emotions, memory and espe-
cially behaviours related to motivation, reward,
wakefulness and attention (Olds & Fobes 1981).
The CSN gives rise to the nigrostriatal pathway
that projects to the putamen and caudate nuclei
of the striatum and is intimately involved in
motor behaviour. Noradrenaline neurones pri-
marily arise in the locus coeruleus and lateral
brain stem tegmentum and project to various
areas of the limbic system, cortex, cerebellum
and spinal cord. These neurones are involved in
control of sympathetic nervous system activity,
anxiety and arousal. Both neurotransmitter
systems, along with 5-HT, have been implicated
in the aetiology of depression (Dunn & Dishman
1991; Cabib & Puglisi-Allegra 1996).
Brain catecholamine metabolism is dramati-
cally increased during periods of stress, includ-
ing physical exercise (Meeusen & De Meirleir
1995). This often leads to partial depletion of cat-
echolamines in various brain regions of rodents.
Although direct evidence of brain catecholamine
depletion is lacking in human subjects, it is
generally believed that alterations in brain
noradrenaline and dopamine are involved in the
neurochemical manifestations of acute stress.
These include behavioural deficits like fatigue,
distress, helplessness, inattention and impaired
motor and cognitive performance. The military
has been very interested in these effects that have
been attributed to deficits in physical and mental
performance that occur in soldiers during the
stress of battle (Owasoyo et al.1992).
The possibility that depletion of these neuro-
transmitters, especially dopamine, may specifi-
cally relate to CNS fatigue during exercise has
also been put forth by several investigators
(Heyeset al.1988; Chaouloff et al.1989; Davis &
Bailey 1997). Dopamine was probably the first
neurotransmitter to be linked to CNS fatigue due
to its well-known role in motor behaviour and
motivation. The specific mechanisms underlying
an effect of dopamine on CNS fatigue remains to
be elucidated. It is hypothesized that decreased