Contents of serotonin and 5-hydroxyindoleacetic acid in the rabbit brain after long-term administration of lithium oxybutyrate

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in rat brain were analysed 24 hours after 7-, 15-, 29- days lithium hydroxybutyrate (LH) injections (10 mg/kg daily). After 7 days the drug reduced 5-HT in hypothalamus and 5-HIAA in the mid brain by 35%. After 15 days LH decreased 5-HT in striatum, hypothalamus by 32 and 17% and 5-HIAA in thalamus, hypothalamus by 28 and 44% respectively. After 29 days LH diminished 5-HT in striatum, hippocampus, amygdala by 24, 29 and 32% and 5-HIAA--in hypothalamus by 42%. The role of adaptative changes and stabilization processes in the central serotoninergic system in mechanism of LH psychotropic effects is discussed.     

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.     

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.     

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 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.     

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.     

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.     

Effect of cold exposure on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in some vertebrate species

1. The changes in 5-HT and 5-HIAA levels were studied in the brain regions of Gerbillus pyramidum, Streptopelia senegalensis aegyptiaca and Agama stellio following exposure to cold. 2. In general, the 5-HT levels increased in the Gerbillus brain parts and decreased in those of Streptopelia. 3. Cold exposure in the Agama brain regions caused a transient decrease in the 5-HT levels of the cerebral hemispheres, midbrain and pons plus medulla after 6 hr and a general increase after 12, 24 and 48 hr. 4. It is concluded that cold exposure may be associated with increased activity of 5-HT ergic neurons and the rate of turnover of 5-HT to 5-HIAA.     

Chronic morphine administration decreases 5-hydroxytryptamine and 2-hydroxyindoleacetic acid content in the brain of rats

To study the effects of chronic morphine treatment on cerebral 5-hydroxytryptamine (5HT) metabolism morphine was administered twice daily for 5 or 8 weeks to male Wistar rats. Control rats were treated with 0.9% NaCl solution for the same period. In rats treated chronically with morphine for 8 weeks the cerebral concentrations of 5HT and 5HIAA were reduced by 12--15% (P less than 0.05) at 26--28 h after the last morphine injection (50 mg/kg s.c.). No such decrease was found in the brain of rats treated with morphine for 5 weeks. A test dose of morphine (30 mg/kg s.c. 2h) increased the cerebral concentration and probenecid-induced accumulation of 5HIAA in the rats treated with morphine for 8 weeks almost as much as in the brain of the control rats. Naloxone (10 mg/kg s.c. 2h) did not cause clear changes in the cerebral 5HT or 5HIAA concentration. These experiments suggest that endogenous opioid mechanisms are concerned in the regulation of 5HT neurons and that prolonged morphine treatment weakens these mechanisms. This weakening of endogenous regulation of 5HT neurons, which, however, still respond to acute morphine administration, might be part of the mechanism of compulsive drug use in narcotic addiction. It is possible that these neurons in dependent individuals do not function optimally without exogenous morphine. A similar phenomenon--weakening of endogenous regulation combined with clear responsivity to exogenous opiates--occurs in the cerebral dopamine neurons of rats treated chronically with narcotic analgesics.     

Effect of prolonged interaction of mice with aggressive and submissive types of behavior on the concentration of serotonin, 5-hydroxyindoleacetic acid and noradrenalin in the brain

As a result of repeated experience of victories and defeats in mice of C57BL/6 line, submissive and aggressive types of behaviour were elaborated, the stabilization of which was accompanied by a change in serotonin and noradrenaline content in various parts of the brain, at least of two kinds. Nonspecific unindirected changes in transmitter' levels found in both groups of animals in comparison with the control, are apparently due to the experience of zoosocial contracts. Changes were also noted connected with specificity of the observed behaviour.     

Microbore liquid chromatography with dual electrochemical detection for the determination of serotonin and 5-hydroxyindoleacetic acid in rat brain dialysates

A microbore liquid chromatographic assay with dual electrochemical detection is described for the determination of serotonin and its metabolite 5-hydroxyindoleacetic acid in rat brain dialysates. The concentration of serotonin in these samples is usually in the low nanomolar range (fmol per 20 μl range). To optimize separation and detection, several adaptations were made to the system with respect to the injection valve, flow-rate of the pump, connections between injector, column and detector, and cell volume of the detector. These aspects are discussed, as well as the procedure developed for optimal peak identification of serotonin and correct estimation of 5-hydroxyindoleacetic acid. The assay allows the measurement of basal serotonin release without the use of a re-uptake inhibitor added to the perfusion fluid.     

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.