Effects of a short-term diet of precooked corn flour on the vaginal cycle, in rats placed in various conditions of environmental illumination

The aim of this research is to study the effects of a diet almost devoid of tryptophan, which is given by a feeding with precooked yellow corn meal (corn mush), on the alterations of the estrous cycle of animals in several conditions of environmental lighting. Indeed, it is known that cerebral serotonin influences the releasing of LH and consequently the ovulation. The different types of environmental lighting are: 1) Natural (alternating Day-Night = L/D). 2) Continuous dark (D/D). 3) Continuous light by sodium steams (L/L sodium). 4) Continuous light by fluorescent neon tubes (L/L neon). The muricide behaviour is studied by comparison rat-mouse. The feeding with precooked yellow corn meal (diet lacking of tryptophan) unchains in the 100% of the observations the CEA (Constant Estrous Anovulatory), and significantly shrinks the estral cycle in the female Wistar Rat in several conditions of environmental lighting.     

Short term diet of precooked corn meal almost lacking in tryptophan and interspecific rat-mouse aggressive behaviour.

The content of tryptophan in a precooked corn meal and in 4 types of selected corn seeds: Zea mays indurata, identata, opaque/2 and Marano synth., has been determined by three different methods: ion-exchange chromatography, spectrofluorometry and spectrophotometry. This content is very low, less than 0.080% d.w. Alimentation for 4 d with a diet composed of precooked corn meal with a tryptophan content less than 0.025% induced the appearance of aggressive-cidal or aggressive non-cidal behaviour towards the mouse in more than half of Wistar rats bred in a room constantly lighted by a sodium steam light. The appearance of this behaviour is probably connected with a decrease in brain serotonin.     

Effect of various environmental illumination modalities on the muricidal behavior of male Wistar rats

The aim of this research is to study the effects of different modalities of environment lighting on the appearance of the muricide behaviour in the Wistar male Rat. Indeed it is known that the exposition of Rats in environment to continuous light determine a reduction of the cerebral content of serotonin, which is known to unchain the muricide behaviour in naturally not muricide Rats. The animals are kept in different situations of environment lighting: 1) L/D = the natural light of the day alternated with the dark of the night; 2) L/L sodium = continuous light emitted by a sodium steam lamp; 3) L/L neon = continuous light issued from fluorescent neon tubes. The muricide behaviour is studied by comparison Rat-Mouse. The results obtained show that the continuous sodium steam light (L/L, sodium) remarkably increase the percentage of the animals which become muricide compared to the control animals bred in natural environment with a normal succession day-night (L/D). On the contrary the percentage is remarkably reduced compared to the control animals in Rats of the same group when these animals are exposed to continuous light issued from fluorescent neon tubes (L/L, neon).     

Different influences of two types of diets commonly used for rats on a series of parameters related to the metabolism of central serotonin and noradrenaline

A commercial chow and a semipurified diet fed for 14 days to Sprague-Dawley male rats kept under standardized conditions of temperature, humidity, and light had different effects on a series of parameters related to the metabolism of central serotonin and noradrenaline. Rats fed the commercial chow had (1) a lower serum level of the six neutral amino acids (valine, isoleucine leucine, tyrosine, phenylalanine, and methionine) known to compete with tryptophan for its entry into the brain, (2) a higher ratio of tryptophan to the sum of the six neutral amino acids, (3) a lower ratio of tyrosine to the other five neutral amino acids, (4) a lower ratio of serotonin to 5-hydroxyindoleacetic acid in hypothalamus, (5) a higher tryptophan hydroxylase activity in raphe nuclei, and (6) a higher content of noradrenaline in hypothalamus. It is suggested that chow fed rats had a more active central serotonin metabolism in hypothalamus than rats fed the semipurified diet.     

Interaction of diet and drugs in the regulation of brain 5-hydroxyindoles and the response to painful electric shock.

The long-term consumption of a tryptophan-poor, corn diet by rats decreases electroshock response thresholds. This hyperalgesia appears to be related directly to diet-induced reductions in the brain concentrations of the putative neurotransmitter, serotinin. Rehabilitating corn-fed animals by feeding them the corn diets supplemented with tryptophan restores brain serotonin and pain thresholds to normal; similarly, injecting the tryptophan-deficient, corn-fed animals with fluoxetine, a drug that blocks the uptake of serotonin into brain neurons, also restores the electroshock response thresholds to control levels. The tryptophan hydroxylase inhibitor, $\text{p}$-chlorophenylalanine, increases the hyperalgesia to electroshock in corn-fed rats and further reduces brain serotonin concentrations. Injection of the amino acid valine, on the other hand, produces hyperalgesia and decreases brain serotonin in casein-fed rats but not in animals fed the corn diet. These data lend support to the hypothesis that serotonin neurons may mediate the sensitivity or reactivity to painful stimuli.     

Cerebrospinal Fluid Concentrations of Tryptophan and 5-Hydroxyindoleacetic Acid in Macaca Mulatta: Diurnal Variations and Response to Chronic Changes in Dietary Protein Intake

In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotonin (5HT) synthesis. However, few studies have examined this relationship in primates (including humans). We therefore studied the effect in monkeys of changes in chronic protein intake on plasma and cerebrospinal fluid (CSF) concentrations of TRP and 5-hydroxyindoleacetic acid (5HIAA), the principal 5HT metabolite. Juvenile male monkeys (Macacca mulatta) consumed for sequential 4-week periods diets differing in protein content (~23% ~ 16% ~10% ~6% protein [%-energy/day]). Each day, food was presented as a morning meal of fruit, and an afternoon meal consisting of a pelleted, commercial diet and fruit. During week 4 on each diet, blood and CSF were sampled diurnally via indwelling catheters. Plasma and CSF TRP varied diurnally and with dietary protein content. On all diets, CSF TRP declined modestly in the morning, and increased in the afternoon; the magnitude of the increments varied directly with dietary protein content. Diurnal variations were absent for CSF 5HIAA; however, CSF 5HIAA varied directly with chronic dietary protein content. We conclude that dietary protein content can chronically influence CSF TRP concentrations in monkeys. The variation in CSF 5HIAA suggests chronic protein intake may influence serotonin synthesis and turnover, perhaps via changes in TRP concentrations.     

Tryptophan feeding adversely influences pregnancy

Additional tryptophan during pregnancy reduces embryo and neonate survival in the golden hamster, $\text{Mesocricetus auratus}$.Relatively small doses of exogenous serotonin have been reported to cause abortions in several vertebrate species (1, 2, 3, 4, 5). Smaller doses reduce litter sizes, increase still births and neonate abnormalities, and otherwise influence pregnancy adversely. These effects are produced by serotonin throughout pregnancy, beginning at implantation (6).The availability of tryptophan is probably the most important rate limiting factor in serotonin synthesis (7). Inasmuch as tryptophan is an essential amino acid and is not synthesized by the body, the diet is the sole source; studies have shown that increases (8) or decreases (9) in dietary tryptophan lead to concomitant changes in serotonin content. Because tryptophan is employed in humans to promote sleep (10, 11, 12) and to decrease appetite (13) we felt it might be important to test whether increased amounts of diet tryptophan can adversely influence pregnancy.     

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.     

EFFECTS OF INGESTION OF A CARBOHYDRATE-FAT MEAL ON THE LEVELS AND SYNTHESIS OF 5-HYDROXYINDOLES IN VARIOUS REGIONS OF THE RAT CENTRAL NERVOUS SYSTEM

—The concentrations of tryptophan, serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in spinal cord and most brain regions increase 2 h after fasted rats begin to consume a carbohydrate-fat meal: indole levels rise in all portions of the brain studied, but the increase is not statistically significant in the hypothalamus and corpus striatum. The rate at which the brain synthesizes 5-hydroxy-indoles (as estimated in vivo by measuring 5-hydroxytryptophan accumulation following an injection of the decarboxylase inhibitor RO4-4602) is also accelerated in all of the regions in which the experimental diet elevates tryptophan, 5-HT and 5-HIAA levels. These observations indicate that the previously reported increase in brain 5-hydroxyindole levels following consumption of a protein-free meal reflects accelerated serotonin synthesis, and occurs within both the cell bodies and the terminals of serotonin-containing neurons. It is possible that diet-induced changes in neuronal serotonin levels influence the quantities of the neurotransmitter released into synapses, either spontaneously or in response to drugs.     

Environmental lighting and muricidal behaviour in the male Wistar rat.

Effects of different conditions of environmental lighting on the appearance of the muricidal behaviour in male Wistar rats have been studied. The animals were kept under different conditions of environmental lighting: 1) natural day light alternated with the dark of the night; 2) sodium, continuous light emitted by a sodium steam lamp; 3) neon, continuous light emitted by fluorescent neon tubes. The continuous sodium steam light increased the percentage of animals becoming muricide when compared to animals bred in a natural environment with a normal succession of day-night lighting. On the contrary, this percentage decreased if the rats of the same group are exposed to continuous light emitted by fluorescent neon tubes. As the exposure of rats to an environment under continuous light causes a reduction of the cerebral content of serotonin, the muricidal behaviour provoked in naturally non-muricide rats by this type of lighting could be related to this depletion.     

Effect of chronic consumption of a high-fat diet on mammary metabolism

Rats have been fed semi-synthetic diets containing 4 and 20% (w/w) corn oil for periods of 9-12 weeks covering two lactations. The mean maternal and pup weights at day-14 of the second lactation on the diets were not significantly different. The milk fatty acids of the rats on the high-fat diet contained 39 mol% linoleic acid and only 20 mol% medium-chain acids compared with over 40% for the low-fat diet. With the exception of "malic" enzyme, none of five enzymes assayed in mammary supernatants was significantly altered by the diet fed. These results suggest that the synthesis of these enzymes in the mammary gland is insensitive to dietary lipid.     

Selective effect of a maize diet in reducing serum and brain tryptophan contents and blood and brain serotonin levels.

The Maize diet used selectively lowers the tryptophan, serotonin and 5-hydroxyindoleacetic acid levels in the central nervous system without affecting catecholamine content. These changes are maximal as early as 48 hours after exposure to the Maize diet. The brain serotonin decrease is reversed to normal when the Maize diet is supplemented with Tryptophan, while nicotinic acid is ineffective. The maize diet seems to be a rapid and selective means of reducing brain serotonin content. The hypothesis that the psychic depression observed in patients with Pellagra may be related to an altered serotonin metabolism is discussed.     

Effect of <Emphasis Type="Italic">p</Emphasis>-Chlorophenylalanine on Tryptophan Hydroxylase in Rat Pineal

KOE and Weissman have demonstrated that p-chlorophenylalanine (pCPA) depletes serotonin in the brain of mammals¹. pCPA induces a variety of behaviour changes in rat, cat and other animals^2,3, presumably because of the depletion of serotonin in the brain. The biochemical mechanism of the depletion remains, however, to be elucidated, although it has been proposed that pCPA might inactivate tryptophan hydroxylase in the brain⁴. We demonstrate here that pCPA does not inactivate tryptophan hydroxylase in rat pineal, although pCPA depletes the serotonin level in the pineal.     

Maize based diets and possible neurobehavioural after-effects among some populations in the world

Maize is a cereal particularly lacking in tryptophan, which is the precursor of serotonin, an important neurotransmitter. Altough complementary foods may eliminate tryptophan deficiency, serotonin deficiency may often continue to exist because of competition made by other Large Neutral Amino Acids (LNAA) against tryptophan for neuron access, since they use the same carrier to cross the blood-brain barrier. Thus serotonin synthesis depends on two variables: the amount of tryptophan and the trp/LNAA ratio (R). “R” is lowest for common maize, low for beans and, as a rule, for most vegetable foods, higher for meat. So, when maize is the preponderant food in the meal, the “R” value lowers and so in parallel serotonin synthesis does. Serotonin deficiency involves several behavioural consequences, such as the tendency towards aggressive behaviour or the religious fanaticism. Among native american populations, these consequences appear, as a rule, positively correlated with maize alimentary dependence (Aztecs appear as those who greatly suffered from serotonin deficiency). In the world these are thinkable for some african populations (i.e. Zulu) or european (i.e. Balkan peoples).     

Rapid repletion of brain serotonin in malnourished corn-fed rats following L-tryptophan injection.

The concentration of tryptophan in serum, and the levels of tryptophan, serotonin (5-HT), and 5-hydroxyindole-acetic acid (5-HIAA) in brain are substantially reduced in rats that consume for 6 weeks a diet in which corn is the only source of protein. Single injections of L-tryptophan (25, 50, or 100 mg/kg) cause dose-related increases in brain tryptophan, 5-HT, and 5-HIAA in corn-fed animals. At each dose, brain tryptophan content rises to a proportionately greater extent in corn-fed rats than in well-nourished controls, even though serum tryptophan concentrations attain higher levels in controls. This difference may reflect the greatly reduced serum concentrations in corn-fed rats of other large neutral amino acids that compete with tryptophan for uptake into the brain (tyrosine, phenylalanine, leucine, isoleucine, and valine). However, the substantial decrease in serum albumin levels also diminishes the binding of tryptophan to serum albumin; thus it is not yet possible to state which of these changes is responsible for the much greater increments in brain tryptophan observed in corn-fed rats after tryptophan injection. The fact that tryptophan administration rapidly restores brain 5-hydroxyindole levels in corn-fed animals suggests that the reductions in 5-HT and 5-HIAA levels associated with this type of malnutrition may be largely caused by inadequate availability of substrate.     

Stimulatory effect of a maize diet on sexual behaviour of male rats

Feeding rats for 4 days with a diet of maize, a staple which is deficient in tryptophan (TP), caused a depletion of brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) without affectin noradrenaline and dopamine content.Addition of TP (2 g/kg of diet) to the TP deficient diet resulted in increased brain 5-HT and 5-HIAA content.Isolated male rats consuming the maize diet, when brought together, showed markedly increased mounting activity, while rats on the maize diet supplemented with TP did not display such a behaviour.These data provide further evidence for the role of the 5-HT system in regulating the sexual behaviour of male rats.     

Low tryptophan diet increases stress-sensitivity, but does not affect habituation in rats

Cerebral dysfunction of 5-HT (serotonin) has been associated with stress response and with affective disorders. Stress alone is insufficient to induce depression, since only a minor proportion of subjects that have experienced stressful life events develop depressive episodes. We investigated whether long-term brain 5-HT depletion induced in rats by a diet with low content of its precursor tryptophan affects stress-responsiveness in rats. Stress-sensitivity was measured through various physiological parameters and by measuring the rats' response to acoustic stimuli. One group of rats was subjected to daily acoustic stimulus sessions for 5 days. Other groups received both immobilization stress and acoustic stimulus sessions daily for either 9 days (chronic experiment) or 1 day (acute experiment). A low tryptophan diet led to decreases in plasma tryptophan levels, low ratio of tryptophan/large neutral amino acid, whole blood 5-HT, and neuronal 5-HT content in the Dorsal and Median Raphe Nuclei, as well as altered c-fos expression in the brain. Without concomitant immobilization, the diet alone did not affect reactivity and habituation to acoustic stimuli, although plasma corticosterone levels, but not the adrenal weights, were increased on day 5. Low tryptophan and chronic immobilization stress together with the acoustic testing procedure increased adrenal weight, plasma corticosterone levels and reactivity to the acoustic stimuli, but not the rate of habituation to acoustic stimuli. These results show that cerebral dysfunction of serotonin achieved through a low tryptophan diet, increases the sensitivity of rats to external and stressful stimuli, but does not impair the capacity to adapt to these stimuli. Accordingly, brain-serotonin modulates reactivity to stress, but not stress coping.     

Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of tryptophan to niacin and of tryptophan to serotonin in rats

The effects of pyrazinamide on the metabolism of tryptophan to niacin and of tryptophan to serotonin were investigated to elucidate the mechanism for pyrazinamide action against tuberculosis. Weanling rats were fed with a diet with or without 0.25% pyrazinamide for 61 days. Urine samples were periodically collected for measuring the tryptophan metabolites. The administration of pyrazinamide significantly increased the metabolites, 3-hydroxyanthranilic acid and beyond, especially quinolinic acid, nicotinamide, N'-methylnicotinamide, and N1-methyl-4-pyridone-3-carboxamide, and therefore significantly increased the conversion ratio of tryptophan to niacin and the blood NAD level . However, no difference in the upper metabolites of the tryptophan to niacin pathway such as anthranilic acid, kynurenic acid and xanthurenic acid was apparent between the two groups. No difference in the concentrations of trytptophan and serotonin in the blood were apparent either. It is suggested from these results that the action of pyrazinamide against tuberculosis is linked to the increase in turnover of NAD and to the increased content of NAD in the host cells.     

The effect of different krill meals fed to laboratory rats on their blood indices.

1. In 102 laboratory rats fed with (a) the krill standardized meal, (b) the krill meal with low chitin content, (c) the casein diet with D,L-methionine, (d) the casein diet with D,L-methionine supplemented with the krill carapace meal, (e) the casein diet with D,L-methionine supplemented with ash from the krill standardized meal and (f) the control diet--"Murigran" standard pelleted feed; the different blood indices were investigated. 2. The mean values of following indices: the number of erythrocytes and leucocytes, the percentage of leucocytes, the corpuscular haemoglobin concentration and red blood cell diameter were similar in all experimental and control groups. 3. The mean values of haematocrit and haemoglobin levels, the mean corpuscular thickness and volume were lower in rats fed with the casein diet with D,L-methionine supplemented with the krill carapace meal than in other groups. 4. All kinds of investigated indices were similar in rats fed with krill meal with low chitin contents, whose parents received the standardized krill meal and no sex differences have been shown here.     

Influence of kynurenines in pathogenesis of cataract formation in tryptophan-deficient regimen in Wistar rats

L-Tryptophan (Trp) is an essential amino acid and its deficiency is involved in various pathologies. In this present investigation an attempt was made to study the role of tryptophan and its metabolites in cataract formation in wistar rats. Rats were divided and maintained in 3 groups, Group A--control; Group B--marginal-tryptophan and Group C--Tryptophan-deficient diet for 3 months. Slit lamp microscope observations indicated lenticular opacities in Group-C (tryptophan-deficient) rats. In the rats that were maintained on tryptophan deficient diet, a decrease in protein content, kynurenines, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-tranferase (GSTs) and tryptophan-fluorescence intensities and an increase in lipid peroxidation indicative of oxidative stress have been observed. The above changes were normalized in the rats on supplementation of 0.05% tryptophan (Group-B) in their diets. These results suggest that tryptophan-deficiency in the diet leads to an overall significant decrease in kynurenines and levels of antioxidant enzymes (except SOD) in ocular tissue with a concomitant lenticular opacification. The results suggest that diet with adequate tryptophan has protective influence and is of immense benefit in mitigating the changes that may otherwise contribute to the lenticular opacities.