Changes in plasma and brain tryptophan and brain serotonin and 5-hydroxyindoleacetic acid after footshock stress

Brain concentrations of tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and plasma amino acids were measured after 15 or 30 minutes of intermittent footshock. Footshock treatment significantly decreased the content of 5-HT in prefrontal cortex and hypothalamus, but not brainstem at 15 min, but the decreases were reversed by 30 min. 5-HIAA, the major catabolite of 5-HT, increased in prefrontal cortex after 15 min, and in prefrontal cortex and hypothalamus after 30 min footshock. 5-HIAA:5-HT ratios were increased at both timepoints in all three brain regions. Concomitant changes in the ratios of 3,4-dihydroxyphenylacetic acid (DOPAC) to dopamine and 3-methoxy,-4-hydroxyphenylethyleneglycol (MHPG) to norepinephrine were also observed. Brain concentrations of tryptophan increased progressively during the footshock in all three brain regions. Plasma concentrations of both tryptophan and tyrosine were also significantly increased, while those of histidine and lysine were decreased. It is possible that the stress-related changes in 5-HT metabolism are due to increased plasma tryptophan, in turn causing increased brain tryptophan and 5-HT synthesis. However, the transient decreases in 5-HT suggest a footshock-induced increase of 5-HT release, depleting existing stores of 5-HT, that are replenished by the increased systemic availability of tryptophan.     

Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet

Rats were trained for 20 days to eat their normal daily meal in a period of 2 hours. On the twentyfirst day they received a diet in which tryptophan was omitted instead of the usual balanced diet. The ingestion of the tryptophan-free diet produced a marked depletion of free serum tryptophan (90%), brain tryptophan (85%), brain 5-HT (58%) and brain 5-HIAA (76%). These changes were almost maximal within 2 hours after food presentation and persisted for more than 24 hours. The mechanism of these changes is discussed.     

The influence of sex and spawning on levels of tryptophan, serotonin and 5-hydroxyindoleacetic acid in the brains of wild brook trout, Salvelinus fontinalis

Levels of tryptophan (TP), serotonin (5-hydroxytryptamine, 5HT) and 5-hydroxyindoleacetic acid (5HIAA) have been determined in the brains of wild brook trout, Salvelinus fontinalis (Mitchill), and brown trout, Salmo trutta L., using high performance liquid chromatography with electrochemical detection. Immediately prior to spawning, adult female brook trout exhibit higher levels of 5HT in the brain than adult males, immature brook trout and immature brown trout. After spawning, the highest levels of TP are found in spent males, which also have higher levels of 5HT in the brain than spent females and immature brook trout. Immature brook trout exhibit higher levels of 5HIAA than prespawning adults. This difference disappears after the spawning season. Serum protein levels and condition factors are lower in spent female brook trout; however, haematocrit values for both sexes remain unchanged after spawning.     

Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers

Brain serotonin synthesis and metabolism (turnover), as indicated by CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), may depend on plasma concentrations of the essential amino acid L-tryptophan (TRP). We investigated the biochemical effects of acute plasma TRP depletion (ATD) in normal volunteers undergoing a 36-h CSF collection via lumbar drain. Six subjects who were in good health were put on a low-TRP diet (160 mg/day) 24 h before lumbar puncture; this diet was continued for the first 22 h of the CSF collection. At hour 22, subjects ingested a TRP-deficient 15-amino acid drink shown previously to deplete plasma TRP. Total plasma TRP, free plasma TRP, and CSF TRP subsequently decreased 86.3, 86.5, and 92.3%, respectively. CSF 5-HIAA decreased by 32.8%. Plasma total and free TRP concentrations were both decreased at approximately 2 h following ingestion of the TRP-free amino acid drink and were lowest approximately 6 h after ATD; CSF TRP and 5-HIAA were decreased at 2.5 h and approximately 4 h after ATD, respectively. CSF TRP was lowest 8.0 h later. CSF 5-HIAA continued to decrease 14 h after the TRP-deficient amino acid drink was given.     

Effect of lithium oxybutyrate on the serotonin and 5-hydroxyindoleacetic acid content in the brain of rabbits

Single administration of lithium hydroxybutyrate (10 mg/kg) to rabbits decreased serotonin and 5-hydroxyindoleacetic acid (5-HIAA) content in the caudate nucleus. The drug administration for 8 days is accompanied by mediator accumulation in the cortex, caudate nucleus, tonsils, hypothalamus, thalamus, and midbrain with parallel reduction in 5-HIAA level in these structures. 15 days of lithium hydroxybutyrate administration lead to the increase of serotonin and 5-HIAA concentration, while 28 days of administration reduced the content of mediator and its metabolite.     

Effect of tryptophan administration on serotonin and 5-hydroxyindoleacetic acid content in the brainstem of Lilly 110140-pretreated rats.

Adult male Sprague-Dawley rats were divided into 3 groups. One group was pretreated with Lilly 110140 (10 mg/kg) 27 hours and again 3 hours before sacrifice while a second group received Lilly 110140 only 3 hours before sacrifice. The third or control group received only equivalent volumes of saline. Animals from each group were administered 25 mg/kg L tryptophan intraperitoneally (i.p.) 0, 30, 60 or 90 minutes before sacrifice. Equivalent elevations in serum and also brainstem tryptophan content were observed in all three groups with the peak observed at 30 minutes. Brainstem serotonin content was significantly elevated in both groups of Lilly 110140-pretreated rats but not in the control group. Brainstem 5-hydroxyindoleacetic acid was significantly elevated after tryptophan administration in the control and the 3 hour and 27 hour, Lilly 110140-pretreated groups but not in the 3 hour Lilly 110140 pretreated group. The results indicate that neither 3 or 3 hours and 27 hours of Lilly 110140 pretreatment appreciably affects the increase in brainstem serotonin synthesis induced by the i.p. administration of 25 mg/kg of L tryptophan.     

Conversion of D- and L-tryptophan to brain serotonin and 5-hydroxyindoleacetic acid and to blood serotonin

Abstract— Intraperitoneal administration of both D- or L-tryptophan elevated the levels of serotonin and 5-hydroxyindoleacetic acid in the brains of hypophysectomized and intact rats. In intact rats, the increase in brain 5-hydroxyindoles was slower after D-tryptophan than after L-tryptophan. Similarly, brain tryptophan rose more slowly after administration of D-tryptophan. The uptake of L-tryptophan from blood into brain was at a rate about one-third that of ³H₂O. D-tryptophan uptake was at 1/25 that of ³H₂O. Brain and liver tryptophan aminotransferase activities were stereospecific for the L-isomer and no evidence could be found for a tryptophan racemase in brain. Evisceration prevented the increase in brain 5-hydroxyindoles following peripheral administration of D-tryptophan administration but not that after L-tryptophan. The serotonin ratios between the two brain regions examined remained constant following administration of either D- or L-tryptophan. On the basis of these results we concluded that the increase in brain 5-hydroxyindoles following administration of L-tryptophan was not dependent upon stress-induced changes in pituitary hormones and that the elevations after D-tryptophan were dependent upon its prior conversion to L-tryptophan via peripheral deamination and subsequent transamination.     

Effect of barbitone sodium and thiopental sodium on brain dopamine, noradrenaline, serotonin and 5-hydroxyindoleacetic acid content in Arvicanthis niloticus

The quantitative estimation of total dopamine (DA), noradrenaline (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in the whole brain tissue of normal Nile grass rat, Arvicanthis niloticus, gives and average of 631 +/- 12 ng DA/g, 366 +/- 12 ng NE/g, 617 +/- 15 ng 5-HT/g and 431 +/- 10 ng 5-HIAA/g fresh brain tissue. The effect of barbitone sodium and thiopental sodium on the total DA, NE, 5-HT and 5-HIAA content in the brain tissue of the Nile grass rat, Arvicanthis niloticus, was studied. The total DA, NE, 5-HT and 5-HIAA contents were determined 5 hr after i.p. injection of different doses of barbitone sodium (20, 40 and 80 mg/ml/100 g body wt) and thiopental sodium (5, 10 and 20 mg/ml/100 g body wt). The effect of different time intervals (1, 10, 30 min, 1, 2.5, 5, 8, 16, 24 and 48 hr) on the total brain DA, NE, 5-HT and 5-HIAA content was investigated after i.p. injection of 40 mg of barbitone sodium and 10 mg of thiopental sodium/ml/100 g body wt. Both barbitone sodium and thiopental sodium caused an increase in DA, NE and 5-HT content and a decrease in 5-HIAA content in the brain tissue of Arvicanthis niloticus. The increase in the whole brain contents of DA, NE and 5-HT after the administration of barbitone sodium and thiopental sodium may be due either to inhibition of transmitter release by an action at the monoamine nerve terminal or to effects causing a decrease in nerve impulse flow. On the other hand, the decrease in 5-HIAA may be due to the decrease in the turnover of 5-HT.     

Effect of the genotype on the serotonin and 5-hydroxyindoleacetic acid content in different sections of the mouse brain

The levels of serotonin and 5-hydroxyindoleacetic acid contents were estimated in hypothalamus, hyppocampus and midbrain of inbred mice of 12 strains. The levels of serotonin and its metabolite in various parts of brain representing different links of its serotoninergic system were shown to be genetically determined. The correlation analysis revealed that there were two, relatively autonomous genetic systems controlling biosynthesis and catabolism of serotonin in brain.     

Neurochemical correlates of behaviour--content of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, tyrosine, dopamine and norepinephrine in four brain parts of the pigeon during behavioural depression following an injection of tryptophan.

Abstract— Pigeons working on a multiple lixed-ratio 50, fixed interval 10 schedule of food reinforcement were injected with l -tryptophan (300mg/kg; I.M.) and killed at various times before, during and after the period of behavioural depression following the administration of this amino acid (0, 25, 50, 90, 170 and 230 min). The levels of tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tyrosine, dopamine and norepinephrine were concurrently measured in 4 specific areas of the brain (telencephalon, diencephalon plus mesencephalon, pons plus medulla-oblongata and cerebellum). The course of the increases in the level of 5-hydroxytryptamine in the telencephalon, and subsequent return to pre-injection levels, was temporally related to the onset of the decreased responding and gradual return to normal rates of responding. Changes in dopamine and norepinephrine were not correlated with the onset of and recovery from the decreased response rates. The data in this paper are discussed in terms of (a) the previously reported work with 5-hydroxytryptophan and (b) the importance of the telencephalic serotonergic system in certain types of behavioural depression.     

Effect of ethanol on the concentration of serotonin in the brain of the rat and the excretion of 5-hydroxyindoleacetic acid

It is found that serotonin content in the brain areas and heart of rats with low alcohol motivation decreases after 5 months of chronic consumption of 48% ethanol solution in a dose of 4 g/kg; in animals with high alcohol motivation serotonin content decreases only in the hypothalamus. Under chronic alcoholization for 1 and 12 months no considerable changes were found in serotonin level of the studied tissues. 60 min after intraperitoneal administration of 20% ethanol solution in a dose of 3 g/kg in intact animals there occurs an increase of serotonin content in the brain hemispheres and heart and its decrease in the hypothalamus; in rat with low alcohol motivation after taking ethanol for 5 months this administration evokes a decrease of serotonin content in the hypothalamus and truncus cerebri; in rats with high alcohol motivation--its decrease in the hypothalamus. Excretion of 5-oxyindoleacetic acid with urine decreases 10 months after alcohol intoxication. When rats were not given ethanol after its chronic taking for 3 months serotonin oxidation was intensified for the first day, which was not observed after 7-month alcoholization of animals.     

Dose-response decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats

Rats fasted 15 hours were treated p.o. with increasing amounts (660 and 1320 mg/kg body weight) of a mixture containing a fixed proportion of seven essential amino acids (L-phenylalanine 13.6%, L-leucine 6.0%, L-isoleucine 12.1%, L-methionine 12.1%, L-lysine 30.3%, L-threonine 10.6%, L-valine 15.2%) and lacking tryptophan. The mixtures produced a dose-response decrease of free (by 34% after the lower dose and by 58% after the higher dose of the mixture) and total (by 10 and 31%) plasma tryptophan and of brain tryptophan (by 38 and 65%), serotonin (by 17 and 41%) and 5-hydroxyindole acetic acid (by 21 and 49%). The mechanisms of these changes are discussed.     

Level of serotonin and 5-hydroxyindoleacetic acid in the brain and immunocompetent organs after immunization]

Twenty minutes after immunization the activation of the serotoninergic system was observed. High level of serotonin metabolism was retained for 24 h after immunization. Change of serotonin level in immunocompetent organs and adrenals took place later than in the brain.     

Effect of heat stress on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in some vertebrate species

1. The variations in 5-HT and 5-HIAA levels following heat exposure and split heat doses were determined in the different brain regions of Gerbillus pyramidum, Streptopelia senegalensis aegyptiaca and Agama stellio. 2. Heat exposure was found to be associated with an increase in the levels of the two indole compounds. 3. The 5-HT concentrations increased markedly in the three species following the first heat dose and decreased following the second dose in the various brain regions except in the cerebellum of Agama. 4. The increased 5-HT levels when animals are exposed to high temperature probably represent a response to activate heat-loss mechanisms and to depress heat production.