Elevated dietary intake of L-tryptophan counteracts the stress-induced elevation of plasma cortisol in rainbow trout (Oncorhynchus mykiss)
Evolutionary Biology Centre, Department of Comparative Physiology, Uppsala University, Norbyvägen 18A, SE-752 36, Sweden
* Author for correspondance (e-mail: Svante.Winberg{at}ebc.uu.se)
Accepted 21 August 2002
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Summary |
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Key words: Serotonin, brain, fish, feed, amino acids, stress, Salmonidae, rainbow trout, Oncorhynchus mykiss, aquaculture
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Introduction |
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Serotonin is synthesized from the essential amino acid L-tryptophan (TRP),
and the first and rate-limiting step in the biosynthesis of 5-HT is the
hydroxylation of TRP to 5-hydroxytryptophan (5-HTP). Since the enzyme
tryptophanhydroxylase (TPH), catalysing the hydroxylation of TRP, does not
seem to be saturated by TRP in vivo, the rate of this reaction
appears to be restricted by TRP availability both in mammals (for a review,
see Boadle-Biber, 1993) and in
teleost fish (Aldegunde et al.,
1998
,
2000
;
Winberg et al., 2001
).
Elevated dietary intake of TRP has been reported to result in increased brain
levels of TRP and elevated rates of 5-HT synthesis and metabolism
(Johnston et al., 1990
;
Aldegunde et al., 1998
,
2000
;
Winberg et al., 2001
). In
mammals, increased functional release of 5-HT following elevated dietary
intake of TRP has been confirmed using microdialyses and in vivo
voltametry (for a review, see Boadle-Biber,
1993
).
Serotonin seems to inhibit aggressive behaviour in all vertebrates, and the
fact that elevated dietary intake of TRP suppresses aggressive behaviour in
rainbow trout Oncorhynchus mykiss
(Winberg et al., 2001)
suggests that elevated dietary intake of TRP in fish also results in increased
synaptic 5-HT release.
The carrier transporting TRP across the bloodbrain barrier is
non-specific, also transporting other large neutral amino acids (LNAA; i.e.
tyrosine, phenylalanine, leucine, isoleucine, valine). Brain levels of TRP
will thus not only depend on plasma levels of TRP, but also on plasma levels
of other LNAA competing for the same carrier
(Boadle-Biber, 1993; Aldegunde
et al., 1998
,
2000
). However, Aldegunde et
al. (2000
) obtained results
suggesting that the competition between TRP and other LNAA for uptake into the
brain is less important in rainbow trout than in mammals. One reason for this
could be that the total plasma pool of TRP is directly available for uptake to
the brain, since TRP is largely found in the free state in rainbow trout
plasma (Rozas et al., 1990
).
In mammals, on the other hand, TRP in plasma is primarily bound to albumin,
and only the small fraction of free TRP is directly available for uptake into
the brain.
The fact that TRP is primarily albumin-bound in blood plasma of mammals
spares it from insulin-mediated uptake by muscle, and as a consequence, a meal
rich in carbohydrate will increase brain 5-HT synthesis by inducing insulin
secretion, which lowers the blood concentration of LNAA other than TRP
(Fernstrom, 1983). Markus et
al. (2000b
) found that a
carbohydrate-rich, protein-poor (CR/PP) food diminished the depressive mood
and cortisol response to controllable as well as uncontrollable
laboratory-induced stress is highly stressprone human subjects. Assuming that
the central 5-HT system is involved, Markus et al.
(2000b
) hypothesised that the
effect of CR/PP food on the stress-induced cortisol response in stressprone
subjects is mediated by a stimulation of the 5-HT pathway connecting the raphe
nucleus to the hippocampus, which inhibits HPA activation
(Deakin, 1991
; Deakin and
Greaff, 1991).
The aim of the present study was to explore whether a stimulation of the brain 5-HT system by dietary supplementation of TRP affects plasma cortisol concentrations in stressed and non-stressed fish. To this end, isolated juvenile rainbow trout were fed feeds containing different levels of TRP for 7 days, after which they were sampled directly or subjected to a standardised stressor.
Acute stress elevates brain TRP concentrations both in mammals
(Curzon et al., 1972;
Dunn, 1988
) and teleost fish
(Winberg and Nilsson 1993a
),
an effect that at least in mammals appears to be mediated by a stress-induced
elevation of sympathetic activity and circulating plasma catecholamines
(Dunn and Welch, 1991
). An
activation of the sympathetic system stimulates lipolysis, resulting in
elevated plasma levels of non-esterified fatty acids, competing with TRP for
binding to albumin and thus elevating the plasma pool of free TRP available
for uptake into the brain (reviewed by
Chaouloff, 1993
). Sympathetic
activation may also increase brain TRP uptake by affecting the permeability of
the bloodbrain barrier (Chaouloff,
1993
). The mechanisms mediating the stress-induced elevation of
brain TRP levels in rainbow trout, where TRP is not transported in the plasma
bound to albumin, are not known.
In order to further clarify the effects of stress on TRP uptake to the brain, plasma and brain levels of LNAA other than TRP were also analysed in the present study.
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Materials and methods |
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Experimental protocol
The experiment was performed in eight 2501 glass aquaria, continuously
supplied with aerated Uppsala tapwater (0.81 min-1, 8-10°C).
Light (12 h:12 h light:dark) was provided by two 20 W warm white fluorescent
tubes placed 100 mm above the water surface. Each aquarium was divided into
four individual 65.5 1 compartments by removable PVC walls. At the start of
the experiment, fish were selected from the holding tank, weighed and
transferred to individual, visually isolated, compartments within the
experimental aquaria. The fish were kept visually isolated and allowed to
acclimate to the experimental environment for 1 week, during which they were
hand-fed commercial trout pellets (Ewos ST40) once a day to satiation. Food
intake of individual fish was quantified by counting the number of pellets
consumed. For quantification of food intake, an individual fish was hand-fed
with one pellet at the time until it rejected three pellets. Pellets not
consumed were removed after feeding. Following this week of acclimation,
commercial feed was exchanged for an experimental feed, supplemented with TRP
at a level corresponding to two (2x feed), four (4x feed) or eight
(8x feed) times the TRP content of the commercial feed, but otherwise
identical to this feed (Table
1). Control fish received feed that was not supplemented with TRP
(1x feed). Fish were fed once a day to satiation and individual food
intake was quantified (as described above). After receiving TRP-supplemented
feed for 1 week, half of the fish in each group were exposed to a standardised
stressor by lowering the water level until the dorsal fin of the fish was
above the water surface. Following 2 h of exposure to this stressor, fish were
killed (see below), and blood and brain tissues collected. Blood samples and
brain tissue were also collected from undisturbed fish, fed control feed
(1x feed) or feed supplemented with TRP (2x, 4x or 8x
feed) and held visually isolated during the experimental period.
|
Blood and brain tissue sampling
Following stress exposure, the fish were anaesthetised (500 mg
1-1 ethyl-m-aminobenzoate methanesulphonate) and blood
(approximately 1 ml) was collected from the caudal vasculature, using a
syringe pre-treated with heparin. Blood samples were rapidly transferred to
Eppendorf tubes and centrifuged at 1500 g for 10 min at
4°C. The blood plasma was then separated, divided into samples, frozen on
dry ice and stored at -80°C. Following blood sampling, the fish were
killed by decapitation, and the brain was rapidly removed (within 2 min) and
divided into telencephalon (excluding olfactory bulbs), hypothalamus
(excluding the pituitary gland), optic tectum, cerebellum and brain stem
(including the medulla and part of the spinal cord). Each brain part was
wrapped into aluminium foil, frozen in liquid nitrogen and stored at
-80°C.
Assays
The frozen brain samples were homogenised in 0.4 mol l-1
ice-cold perchloric acid (PCA) containing 0.2% EDTA and 40 ng ml-1
epinine (deoxyepinephrine, the internal standard), using a
PotterElvehjem homogeniser (optic tectum, cerebellum and brain stem) or
an MSE 100 W ultrasonic disintegrator (telencephalon and hypothalamus).
Brain levels of 5-HT and 5-HIAA were quantified using high-performance
liquid chromatography (HPLC) with electrochemical detection, as described by
Øverli et al. (1999).
Plasma and brain levels of TRP were analysed using the same HPLC system with a
mobile phase consisting of 75 mmol l-1 sodium phosphate in
deionized water containing 15% methanol and brought to pH 3.1, and an
oxidation potential of 600 mV (Winberg et
al., 2001
). Plasma samples used for TRP analysis were
deproteinized and extracted in 0.4 mol l-1 PCA containing 0.2%
EDTA.
The amount of other LNAA was measured using HPLC and fluorometric detection
of the derivative formed between the amine and naphtalene-2,3-dicarboxaldehyde
(NDA), as described by de Montigny et al.
(1987). The derivatization
consisted of adding 50 µl of brain or plasma extract to 200 µl of borate
buffer (0.1 mol l-1, pH 10.1) followed by the addition of 50 µl
of sodium cyanide (25 mmol l-1) and 200 µl NDA (10 mmol
l-1). After a reaction time of 15 min, the reaction mixture was
analyzed by gradient-elution HPLC. The HPLC apparatus consisted of a multiple
solvent delivery system (CM 4000, LDC/Milton Roy, Riviera Beach, USA), a
refrigerated autoinjector (CMA/2000, Carnegie Medecin, Stockholm, Sweden), a
Nucleosil RP-18 column (3 µm particle size, 0.4 cm i.d.x10 cm length;
Duren, Germany), and a JASCO FP-920 fluorescense Detector (JASCO Corporation,
Tokyo, Japan) set at excitation/emission wavelengths of 420/490 nm. The mobile
phase was delivered at 1 ml min-1 and consisted of 50 mmol
l-1 potatium phosphate in deionised water containing 10 %
tetrahydrofuran, pH 6.8 (solvent A), or 55% acetonitrile and 10% methanol, pH
6.8 (solvent B). A linear gradient from 100% solvent A/0% solvent B to 40%
solvent A/60% solvent B over a 60 min period was used. Samples were analysed
by comparison with standard solutions of known concentrations, and corrected
for recovery of the internal standard (chlorophenylalanine, 10 mmol
l-1) using the HPLC software BORWIN (FMPS developpements,
France).
Cortisol analysis was performed directly on rainbow trout plasma without
extraction, using a validated radioimmunoassay (RIA) modified from Olsen et
al. (1992), as described by
Winberg and Lepage (1998
).
Statistics
All data are presented as means ± S.E.M. Effects of feed and
treatment (stress versus non-stress) were examined using two-way
analysis of variance (ANOVA) followed by the least significant difference
(LSD) post-hoc test. Correlations were tested using Spearman
rank-correlation coefficients. All statistical analyses were performed using
STATISTICA statistical software.
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Results |
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Blood plasma TRP, LNAA and cortisol levels
Stressing the fish by lowering the water levels in the aquaria had a
significant effect on plasma [cortisol] (F1,41=5.82,
P=0.0204); fish subjected to stress showed elevated plasma [cortisol]
compared to undisturbed fish (Fig.
2). The stressed fish fed control feed displayed significantly
higher plasma [cortisol] (P=0.0002) than non-stressed controls. There
was no significant effect of feeding TRP-feed on plasma cortisol levels but
there was a significant interaction between treatment (stress versus
non-stress) and feed (F3,41=3.96, P=0.0144).
Basal plasma [cortisol] was elevated after feeding the fish TRP-supplemented
feed, and non-stressed fish fed 2x, 4x and 8x TRP-feed
showed significantly higher plasma [cortisol] than non-stressed fish fed
control feed (P=0.0416, P=0.0288, P=0.0071,
respectively) (Fig. 2). By
contrast, stressed fish fed 4x TRP-feed displayed significantly lower
plasma [cortisol] than stressed fish fed control feed (P=0.0357).
Interestingly, in fish fed 4x and 8x TRP-feed, stress did not
result in any significant elevation of plasma [cortisol]
(Fig. 2).
|
Dietary TRP supplementation had an effect on plasma [TRP] (F3,38=11.21, P<0.0001), plasma [TRP] increasing with increasing feed TRP levels (Table 2). Since elevated dietary TRP caused an increased plasma [TRP] without affecting [LNAA] in the plasma, feeding the fish TRP-supplemented feed had a significant effect on plasma [TRP]/[LNNA] ratios (F3,39=10.24, P<0.0001) (Table 2). Stress had no significant effect on [TRP], [LNAA] or [TRP]/[LNAA] in the plasma (Table 2). Stress or dietary TRP did not have significant effects on the plasma concentration of individual LNAAs, other than TRP (i.e. leucine, isoleucine, phenylalanine, tyrosine or valine, data not shown).
|
Brain [TRP], [LNAA], [5-HIAA] and [5-HT], and brain [5-HIAA]/[5-HT]
ratios
Stress had a significant effect on [TRP] in the optic tectum
(F1,39=7.68, P=0.0085) and brain stem
(F1,38=4.24, P=0.0465), stressed fish showing
elevated [TRP] (Fig. 3C,D).
Moreover, feeding the fish TRP-supplemented feed had a significant effect on
[TRP] in the telencephalon (F3,36=2.88,
P=0.0492), hypothalamus (F3,40=4.60,
P=0.0074) and optic tectum (F3,39=2.30,
P=0.0085) (Fig. 3A-C).
TRP supplementation resulted in elevated [TRP] in these brain areas and a
similar but non-significant trend (F3,38=0.2.68,
P=0.0605) was also observed in brain stem
(Fig. 3D). Stressed fish fed 4X
(P=0.0245) and 8X TRP-feed (P=0.0243) displayed
significantly higher telencephalic [TRP] than stressed fish fed control feed
(Fig. 3). Similarly, in the
hypothalamus, brain stem and optic tectum [TRP] was significantly higher in
stressed fish fed 8X TRP-feed (P=0.0079, P=0.0103,
P=0.0121, respectively) than in stressed fish fed control feed
(Fig. 3B-D). Moreover, in the
hypothalamus, undisturbed fish fed 8X TRP-feed showed higher [TRP] than
undisturbed fish fed control feed (P=0.0198)
(Fig. 3B). In optic tectum,
stressed fish fed 8X TRP-feed had significantly higher [TRP] than non-stressed
fish fed 8X TRP-feed (P=0.0301)
(Fig. 3C).
|
Brain [TRP]/[LNAA] ratios were not significantly affected by stress or dietary TRP in any part of the brain (Table 3). Similarly, there were no significant effects of stress or dietary TRP on brain [LNAA] (Table 3), or on the concentration of individual LNAAs, other than TRP (i.e. leucine, isoleucine, phenylalanine, tyrosine or valine; data not shown).
|
Highly significant correlations were found between plasma [TRP] and [TRP] in the telencephalon (rs=0.45, P=0.0027), hypothalamus (rs=0.52, P=0.0003), brain stem (rs=0.44, P=0.0033) and optic tectum (rs=0.39, P=0.0104). Similar significant correlations were also observed between plasma [TRP]/[LNAA] ratios and [TRP] in telencephalon (rs=0.73, P=0.0036), hypothalamus (rs=0.68), P=0.0005), brain stem (rs=0.69, P=0.0138), and optic tectum (rs=0.78, P=0.0236).
[5-HT] was not affected by stress or dietary TRP supplementation in any part of the brain (Table 3).
Stress had a significant effect on [5-HIAA] in the telencephalon (F1,37=16.82, P=0.0002), hypothalamus (F1,40=16.94, P=0.0002), and brain stem (F1,32=2.28, P=0.0366), and a similar but not significant trend was observed in the optic tectum (F1,41=3.17, P=0.0826) (Table 3). In each of these brain parts, stressed fish displayed elevated [5-HIAA] as compared to undisturbed fish. However, hypothalamic [5-HIAA] levels were significantly increased only in stressed fish fed control feed (P=0.0425) (Table 3).
Stress had a significant effect on [5-HIAA]/[5-HT] ratios in the telencephalon (F1,37=15.67, P=0.0004), hypothalamus (F1,40=8.85, P=0.0049) and brain stem (F1,32=11.20, P=0.0021) (Fig. 4A,B,D), but there was no significant effect in the optic tectum (Fig. 4C). In each of these brain parts, stressed fish displayed elevated [5-HIAA]/[5-HT] ratios as compared to undisturbed fish. In the brain stem, stressed fish fed control feed showed an elevation of [5-HIAA]/[5-HT] ratios as compared to undisturbed controls (P=0.0130). Telencephalic [5-HIAA]/[5-HT] ratios were significantly elevated in stressed fish fed 2X and 4X TRP-feed compared to undisturbed controls fed 2X and 4X TRP-feed (P=0.0339 and P=0.0096, respectively). There was no significant effect of elevated dietary TRP levels on the brain [5-HIAA]/[5-HT] ratio, but there was a tendency towards an elevated [5-HIAA]/[5-HT] ratio in all brain areas of fish fed TRP-supplemented feed (Fig. 4).
|
A correlation was found in stressed fish between [TRP] and [5-HIAA]/[5-HT] only in the telencephalon (rs=0.53, P=0.0097).
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Discussion |
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In accordance with previous studies, stress resulted in elevated brain
[5-HIAA]/[5-HT] ratios (Winberg and
Nilsson, 1993b; Winberg and
Lepage, 1998
; Øverli et
al., 1999
; Höglund et
al., 2000
). The central 5-HT system has been suggested to
stimulate the HPI axis, and Winberg et al.
(1997
) showed that treatment
with 8-OH-DPAT, a specific 5-HT1A-receptor agonist, results in a
dose-dependent elevation of plasma [cortisol] in dorsal aorta-cannulated
rainbow trout. In mammals, 5-HT terminals make synaptic contact with
corticotropin-releasing hormone immunoreactive neurons within the hypothalamic
paraventricular nucleus (Liposits et al.,
1987
), and treatment with 5-HT precursors, such as TRP or 5-HTP,
as well as 5-HT receptor agonists, has been reported to stimulate HPA axis
activity, elevating plasma levels of glucocorticoids
(Chaouloff, 1993
). Thus, the
elevation of plasma [cortisol] in non-stressed fish fed TRP-supplemented feed
observed in the present study could well have been mediated by a stimulation
of the brain 5-HT system.
In this light, the observation that supplementary dietary TRP attenuated the stress-induced elevation of plasma [cortisol] may seem contradictory. One explanation for this effect could of course be elevated negative feedback as a result of increased basal plasma [cortisol], as indicated by elevated plasma [cortisol] in non-stressed fish receiving TRP-supplemented feed. However, even though significant, the elevation of plasma [cortisol] in non-stressed fish fed TRP-supplemented feed was small, suggesting that other mechanisms are also involved in mediating the effects of TRP on stress responsiveness.
The facilitating effects of 5-HT agents on plasma cortisol concentrations
may not be in conflict with the observation that, under acute stress, 5-HT
activity could improve ability to cope with stress and contribute to reducing
a cortisol response (Markus et al.,
2000b; Höglund et al.,
2002
). The serotonergic system is not a unitary system and
different 5-HT pathways seem to be involved in both initiating and terminating
the adrenocortical stress response in mammals
(Deakin and Graeff, 1991
;
Graeff et al., 1996
). For
instance, 5-HT pathways terminating in the hippocampus are believed to inhibit
HPA axis activity (Summers et al.,
1998
; Markus et al.,
2000b
). Recently, Höglund et al.
(2002
) reported that treatment
with the 5-HT1A agonist, 8-OH-DPAT, elevates plasma [cortisol] in
undisturbed Arctic charr Salvelinus alpinus, whereas the same drug,
if administered in connection with stress, suppresses the stress-induced
elevation of plasma [cortisol].
Moreover, treatments elevating plasma [TRP] and/or [TRP]/[LNAA] ratios have
been reported to counteract stress-induced elevations of plasma cortisol in
mammals (Morméde and Dantzer,
1979), including humans (Markus et al.,
1998
,
1999
,
2000a
,
b
). For instance, in pigs
preloaded with 50-200 mg kg-1 TRP, activation of the HPA axis in
response to the experience of an unfamiliar environment, in combination with
unavoidable shocks, is decreased
(Morméde and Dantzer,
1979
). Moreover, carbohydrate-rich, protein-poor food, which
causes an elevation of plasma [TRP]/[LNAA] ratios, prevents the elevation of
plasma cortisol induced by uncontrollable
(Markus et al., 1998
) and
controllable stress (Markus et al.,
1999
) in stress-prone human subjects. Similarly, a diet enriched
in
-lactalbumin, a TRP-rich protein, reduces depressive mood and plasma
cortisol concentrations in stress-prone subjects under acute stress
(Markus et al., 2000a
).
In a recent study we showed that dietary supplementation of TRP for 7 days
results in an inhibition of aggressive behaviour in rainbow trout, whereas 3
days of TRP supplementation have no effect on aggressive behaviour
(Winberg et al., 2001). Since
the effect of elevated dietary TRP intake on 5-HT synthesis and release could
be expected to be very rapid, other mechanisms are likely to be involved in
mediating effects of elevated dietary TRP on aggressive behaviour, and
possibly also in mediating the effects of TRP on stress responsiveness, since
in the present study the fish were fed TRP-supplemented feed for 7 days.
Interestingly, the anti-depressive effect of specific 5-HT re-uptake
inhibitors (SSRI), such as fluoxetine (Prozac), is only evident after
long-term treatment (Mongeau et al.,
1997
). Initially SSRI treatment markedly decreases the firing
activity of 5-HT neurones. However, the firing rate of 5-HT neurones recovers
if the SSRI treatment continues for 1-3 weeks, and this recovery seems to be
associated with a desensitisation of 5-HT1A somato-dendritic
autoreceptors (Mongeau et al.,
1997
; Nutt et al.,
1999
). Moreover, long-term SSRI treatment has been found to
desensitise presynaptic 5-HT autoreceptors located at nerve terminals, and to
increase the baseline level of 5-HT in the hippocampus
(Kreiss and Lucki, 1995
).
Possibly, long-term effects of elevated dietary intake of TRP on stress
responsiveness and aggression in rainbow trout are mediated by similar
mechanisms, resulting in elevated 5-HT release in areas of the trout brain
homologous to the mammalian hippocampus.
According to Northcutt and Davis
(1983), the dorsal and ventral
parts of the dorsal area of the teleostean telencephalon are a putative
homologue of the mammalian hippocampus. Notably, in the present study,
following 7 days of TRP supplementation, a significant correlation between
[TRP] and [5-HIAA]/[5-HT] ratios was observed only in the telencephalon of
stressed fish.
Serotonin may also suppress HPI axis activity by inhibiting central
norepinephrine (NE) activity. In mammals, NE stimulates hypothalamic
corticotropin-releasing hormone, which in turn has a stimulatory effect on NE
activity (Huether, 1996),
creating a positive feedback loop, which seems to be counterbalanced by an
inhibition of the NE system by 5-HT
(Aston-Jones et al., 1991
;
Engberg, 1992
). The central NE
system has been suggested to stimulate HPI axis activity in teleost fish
(Øverli et al., 1999
;
Höglund et al., 2000
).
Consequently, by elevating brain 5-HT activity, increased dietary intake of
TRP may suppress the stress-related activation of the brain NE system, and by
that inhibit the stressed-induced activation of the HPI axis.
As expected, feeding the fish TRP-supplemented feed resulted in elevated
plasma [TRP]. Plasma [TRP]/[LNAA] ratios were also elevated in fish fed
TRP-supplemented feed since the amount of other LNAA were similar in the feeds
(Table 1). Increasing dietary
levels of TRP were also reflected in elevated brain [TRP] and a
non-significant trend towards increased brain [TRP]/[LNAA]. Moreover, as
reported previously, stress resulted in an elevation of brain [TRP] (Winberg
and Nilsson 1993a,
b
) but had no effect on brain
levels of other LNAA, nor did stress affect plasma levels of TRP, other LNAA,
or plasma [TRP]/[LNAA]. Thus, since in rainbow trout the TRP plasma pool is
not protein-bound (Rozas et al.,
1990
) and is completely available for uptake to the brain, a
stress-mediated effect on the availability of TRP for uptake to the brain
could not explain the stress-induced elevation of brain [TRP]. It is more
likely that the elevation of brain [TRP] observed in stressed rainbow trout is
mediated by stress-induced effects on the bloodbrain barrier
permeability. In mammals, the increase in brain [TRP] during stress seems to
involve the sympathetic nervous system, and is attenuated by the
ß-adrenergic receptor antagonist, propranolol, but not by the
-adrenoreceptor antagonist phentolamine
(Dunn and Welch, 1991
). Dunn
(1999
) showed that treatment
with the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine
(L-NAME) attenuates the stress-induced elevation of brain [TRP] in mice,
suggesting that NO is involved in mediating an elevation of brain [TRP] in
response to stress in mammals.
In conclusion, the results of the present study show that dietary
supplementation of TRP for 7 days attenuates the stress-induced increase in
plasma cortisol levels in juvenile rainbow trout, an effect that is most
likely to be mediated by the brain serotonergic system. Supplementing feed
with TRP could be a promising strategy in aquaculture management, not only
making the fish more stress-resistant, but also decreasing aggressive
behaviour, and thus the tendency to develop strong dominance hierarchies,
resulting in stress, reduced disease resistance and highly variable growth
rates of fish in aquaculture (Winberg et
al., 2001).
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Acknowledgments |
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References |
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