The effects of 5-hydroxytryptophan on carrageenan-induced mouse paw oedemas / Efeito de 5-hidroxitriptofano no edema de pata de camundongo induzido por carragenina

ABSTRACT Objective 5-Hydroxytryptophan is the precursor compound of serotonin biosynthesis. The oral absorption of 5-Hydroxytryptophan is close to 100% and, unlike serotonin, it crosses the blood-brain barrier freely. 5-Hydroxytryptophan has been used as a food supplement for many years to treat anxiety and depression. Recent studies have shown that 5-Hydroxytryptophan suppresses the pro-inflammatory mediators and is effective in some inflammatory diseases, such as arthritis and allergic asthma. However, the role of 5-Hydroxytryptophan supplements on acute peripheral inflammation has not been investigated yet. In this study, the in vivo anti-inflammatory activity of 5-Hydroxytryptophan was evaluated with a carrageenan-induced paw oedema test in mice. Methods For the investigation of the acute antiinflammatory activity, single oral doses of 5-Hydroxytryptophan (1.5, 5 and 20mg/kg) were given to mice 1.5 hours prior to the carrageenan test. For chronic activity, the same oral doses were administered daily for two weeks prior to the carrageenan test on the 14th day. To induce inflammation, 0.01mL of 2% carrageenan was injected into the paws of mice. Results Supplementation with 5-Hydroxytryptophan significantly reduced inflammation in a dose-independent manner which was irrespective of the duration of exposure (per cent inhibition in acute experiments was 35.4%, 20.9%, 24.0%, and per cent inhibition in chronic experiments was 29.5%, 35.3%, 40.8% for the doses of 1.5, 5, and 20mg/kg, respectively). Conclusion Our findings demonstrate for the first time that 5-HTP supplements have the potential of suppressing the measures of acute peripheral inflammation. It is suggested that, apart from several diseases where serotonin is believed to play an important role, including depression, patients with inflammatory conditions may also benefit from 5-HTP.

RESUMO Objetivo O 5-hidroxitriptofano (5-HTP) é o composto precursor da biossíntese da serotonina. A absorção oral do 5-HTP é próxima a 100% e, ao contrário da serotonina, atravessa a barreira hematoencefálica livremente. O 5-HTP tem sido usado como suplemento alimentar por muitos anos na ansiedade e na depressão. Estudos recentes demonstraram que o 5-HTP suprime os mediadores pró-inflamatórios e é eficaz em algumas doenças inflamatórias, como artrite e asma alérgica. No entanto, o papel dos suplementos de 5-HTP na inflamação periférica aguda ainda não foi investigado. Neste estudo, a atividade anti-inflamatória in vivo do 5-HTP foi avaliada por meio do teste de edema de pata induzido por carragenina em ratos. Métodos Para a atividade aguda, doses orais únicas de 5 -HTP (1,5, 5 e 20 mg/kg) foram dados aos ratos 1,5 horas antes do teste da carragenina. Para a atividade crônica, as mesmas doses orais foram dadas cada dia durante duas semanas antes do teste da carragenina no 14º dia. 0,01ml da carragenina a 2% foi injetado nas patas dos ratos a fim de induzir a inflamação. Resultados A suplementação com 5-HTP reduziu significativamente a inflamação de uma maneira independente da dose, que foi independente da duração da exposição (por cento de inibição em experimentos agudos; 35,4%, 20,9%, 24,0% e por cento de inibição em experimentos crônicos; 29,5%, 35,3%, 40,8% para as doses de 1.5, 5 e 20 mg/kg respectivamente). Conclusão Nossas conclusões demonstram pela primeira vez que os suplementos de 5-HTP têm potencial para suprimir os sintomas de inflamação periférica aguda. É sugerido que, além de várias doenças em que se acredita que a serotonina tem uma função importante, incluindo a depressão, os pacientes com doenças inflamatórias também podem se beneficiar do 5-HTP.

Short communication: Supplementation of colostrum and milk with 5-hydroxy-l-tryptophan affects immune factors but not growth performance in newborn calves.

In ruminants, colostrum is the main source of immunoglobulins for the newborn animal, conferring immune protection until the immune system becomes active and able to synthesize its own immunoglobulins. Serotonin (5-HT), a biogenic amine derived from tryptophan, has stimulatory effects on many physiological processes, including components of the innate (mastocytes, eosinophils, and natural killer cells) and adaptive (T and B lymphocytes) immune systems. Based on the known effects of 5-HT on the immune system, we hypothesized that increased concentrations of 5-HT, through administration of its precursor 5-hydroxy-l-tryptophan (5-HTP), may positively affect development of the calf's immune system and therefore support health and growth performance during the first weeks of life. Eighteen calves were randomly assigned to 1 of 2 experimental groups (control and 5-HTP), resulting in n = 9 per treatment group. Both groups received 2 colostrum meals from a common pool of colostrum. Thereafter, calves were fed milk replacer twice daily for 30 d. In the 5-HTP group, colostrum and milk replacer were supplemented with 1.5 mg of 5-HTP/kg of birth weight during the first 15 d after birth. Body weight was recorded at birth and on d 5, 10, 15, and 30 after birth. Blood samples were collected every morning (0800 h) before feeding from birth until d 5 and then on d 7, 9, 11, 13, 15, and 30 after birth. Serum 5-HT concentrations were increased as a consequence of the 5-HTP supplementation. Plasma immunoglobulin G concentrations did not differ between groups throughout the experimental period. The blood mRNA abundance of several factors related to the innate and adaptive immune system [nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), serum amyloid A-1 (SAA1), chemokine C-C motif ligand 5 (CCL5), cyclooxygenase 2 (PTGS2), haptoglobin (HP), and IL-1ß] were increased in calves supplemented with 5-HTP. Supplementation of 5-HTP did not affect any of the measured metabolites (fatty acids and glucose) or minerals (calcium and magnesium) or milk feed intake, feed conversion ratio, and growth. In conclusion, 5-HTP supplementation induced an increase of 5-HT concentrations in blood and caused an increase in mRNA abundance of several factors related to the innate and adaptive immune systems, which might increase the protection of the calf against external agents.

Preliminary fMRI findings concerning the influence of 5-HTP on food selection.

OBJECTIVE: This functional magnetic resonance imaging study was designed to observe how physiological brain states can alter food preferences. A primary goal was to observe food-sensitive regions and moreover examine whether 5-HTP intake would activate areas which have been associated with appetite suppression, anorexia, satiety, and weight loss. METHODS AND PROCEDURE: Fourteen healthy male and female participants took part in the study, of which half of them received the supplement 5-HTP and the rest vitamin C (control) on an empty stomach. During the scanning session, they passively observed food (high calories, proteins, carbohydrates) and nonfood movie stimuli. RESULTS: Within the 5-HTP group, a comparison of food and nonfood stimuli showed significant responses that included the limbic system, the basal ganglia, and the prefrontal, temporal, and parietal cortices. For the vitamin C group, activity was mainly located in temporal and occipital regions. Compared to the vitamin C group, the 5-HTP group in response to food showed increased activation on the VMPFC, the DLPFC, limbic, and temporal regions. For the 5-HTP group, activity in response to food high in protein content compared to food high in calories and carbohydrates was located in the limbic system and the right caudomedial OFC, whereas for the vitamin C group, activity was mainly located at the inferior parietal lobes, the anterior cingulate gyri, and the left ventrolateral OFC. Greater responses to carbohydrates and high calorie stimuli in the vitamin C group were located at the right temporal gyrus, the occipital gyrus, the right VLPFC, whereas for the 5-HTP group, activity was observed at the left VMPFC, the parahippocampal gyrus bilaterally, the occipital lobe, and middle temporal gyri. DISCUSSION: In line with the hypotheses, 5-HTP triggered cortical responses associated with healthy body weight as well as cerebral preferences for protein-rich stimuli. The brain's activity is altered by macronutrients rich or deprived in the body. By reading the organisms physiological states and combining them with memory experiences, it constructs behavioral strategies steering an individual toward or in opposition to a particular food.

Rumination time and reticuloruminal temperature as possible predictors of dystocia in dairy cows.

The objectives of this study were to explore changes of rumination time and reticuloruminal pH and temperature of dairy cows and heifers (means ± standard deviation; age = 5.8 ± 1.9; parity = 2.7 ± 1.4; body condition score = 3.2 ± 0.2) with eutocic (EUT, n = 10) and dystocic calving (DYS, n = 8). The recording period lasted from 3 d before calving until 7 d in milk. For the comparison of rumination time and reticuloruminal characteristics between groups, time to return to baseline (the time interval required to return to baseline from the delivery of the calf) and area under the curve (AUC; both for prepartum and postpartum periods) were calculated for each parameter. Rumination time decreased from baseline 28 h before calving both for EUT and DYS cows; after 20 h before calving, it decreased to 32.4 ± 2.3 and 13.2 ± 2.0 min/4 h between 8 and 4 h before delivery in EUT and DYS cows, respectively, and then it decreased below 10 and 5 min during the last 4 h before calving. Until 12 h after delivery, rumination time reached 42.6 ± 2.7 and 51.0 ± 3.1 min/4 h in DYS and EUT dams, respectively; however, AUC and time to return to baseline suggested lower rumination activity in DYS cows than in EUT dams for the 168-h postpartum observational period. Reticuloruminal pH decreased from baseline 56 h before calving both for EUT and DYS cows, but did not differ between groups before delivery. Reticuloruminal pH showed a decreasing tendency and clear diurnal variation after calving for both EUT and DYS cows, with slightly higher AUC values in DYS cows. In DYS cows, reticuloruminal temperature decreased from baseline 32 h before calving by 0.23 ± 0.02°C, whereas in EUT cows such a decrease was found only 20 h before delivery (0.48 ± 0.05°C). The AUC of reticuloruminal temperature calculated for the prepartum period was greater in EUT cows than in DYS cows. During the first 4 h after calving, reticuloruminal temperature decreased from 39.68 ± 0.09 to 38.96 ± 0.10°C and from 39.80 ± 0.06 to 38.81 ± 0.08°C in EUT and DYS cows, respectively, and reached baseline levels after 35.4 ± 3.4 and 37.8 ± 4.2 h after calving in EUT and DYS cows, respectively. Based on our results, continuous monitoring of changes in rumination time and reticuloruminal temperature seems to be promising in the early detection of cows with a higher risk of dystocia. Depressed rumination activity of DYS cows after calving highlights the importance of the postpartum monitoring of cows experiencing difficulties at calving. The effect of dystocia on postpartum reticuloruminal pH was not pronounced.

Increased serum serotonin improves parturient calcium homeostasis in dairy cows.

Hypocalcemia in dairy cows is caused by the sudden increase in calcium demand by the mammary gland for milk production at the onset of lactation. Serotonin (5-HT) is a key factor for calcium homeostasis, modulating calcium concentration in blood. Therefore, it is hypothesized that administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, can increase 5-HT concentrations in blood and, in turn, induce an increase in blood calcium concentration. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (C group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before the estimated parturition and ceased the day of parturition, resulting in at least 4 d of infusion (8.37 ± 0.74 d of infusion). Until parturition, blood samples were collected every morning before the infusions, after parturition samples were taken daily until d 7, and a final sample was collected on d 30. Milk yield was recorded during this period. No differences between groups were observed for blood glucose, magnesium, and ß-hydroxybutyrate. Cows receiving the 5-HTP infusion showed an increase in fatty acid concentrations from d -3 to -1 before parturition. Serum 5-HT concentrations were increased at d -4 related to parturition until d 5 postpartum in the 5-HTP group compared with the C group. In addition, cows from the 5-HTP group had increased 5-HT concentrations in colostrum, but not in mature milk, on d 7 postpartum. Serum calcium concentrations decreased in both groups around parturition; however, calcium remained higher in the 5-HTP group than in controls, with a significant difference between groups on d 1 (1.62 ± 0.08 vs. 1.93 ± 0.09 mmol/L in control and 5-HTP groups, respectively) and d 2 (1.83 ± 0.06 vs. 2.07 ± 0.07 mmol/L in control and 5-HTP groups, respectively). Additionally, colostrum yield (first milking) was lower in the 5-HTP group compared with the C group, but without consequences on colostrum IgG concentrations. Milk yield did not differ between groups during the rest of the experiment. The study data were consistent with the concept that infusion of 5-HTP to dairy cows increases blood 5-HT concentrations, which in turn is a significant regulatory component in the chain of effectors that affect calcium status around parturition, hence the occurrence of clinical or subclinical hypocalcemia.

Expression of arginine vasotocin and estrogen receptor alpha (ERα) in the shell gland altered by the specific phase relations of neural oscillations affects the reproductive physiology of Japanese quail.

In order to study the effect of specific phase relation of neural oscillations on reproductive regulation and the response of AVT (the avian homologue of mammalian AVP) the expression of AVT in the shell gland was monitored in sexually immature quail. In this study 3-week-old female Japanese quail were administered with serotonin precursor, 5-hydroxytryptophan followed by the dopamine precursor, l-dihydroxyphenylalanine at interval of 8h and 12h daily over a period of 13days. At thirty two days post treatment, a significant decrease in gonadal activity was seen in 8h quail although 12h quail exhibited an increase as compared to controls. A significant decrease in plasma estradiol level was noted in 8h quail while 12h exhibited no significant difference compared to controls. To address the relative roles of estrogen mediated action we also investigated estrogen receptor alpha (ER-α) expression and localization in the shell gland by visualizing it through confocal immuno-fluorescence microscopy. Results indicate increased expression of immunoreactive (ir)-AVT (myometrium), ir-ER-α (epithelial cells of endometrial region), along with significant increase in hypothalamic, plasma and shell gland AVT and a rapid increase in egg laying thus maintaining full breeding condition in 12h while low expression of ir-AVT and ir-ER-α was observed in 8h quail along with a significant decrease in hypothalamic, plasma and shell gland AVT with the suppression of gonads thereby stopping the egg-laying behaviour was noted. These findings not only suggest the modulation of gonadal development by changing the specific phase relation of neural oscillations but also demonstrate a parallel relation of AVT and gonadal activity in both conditions. It is concluded that the egg laying performance in response to AVT is regulated by the temporal phase relationship of neurotransmitters, and in part, this effect appears to be estrogen dependent.

Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats.

An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0.048). These results show that increasing 5-HT biosynthesis during the transition from pregnancy to lactation could be a potential therapeutic target to explore for prevention of subclinical and clinical hypocalcemia.

Effect of magnesium chloride on psychomotor activity, emotional status, and acute behavioural responses to clonidine, d-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan.

BACKGROUND: The beneficial effects of magnesium (Mg) salts on central manifestations of Mg deficiency are well known. Mg replacement therapy can be effective to prevent some of the serious depression-like and anxiety-related behaviour sequelae of Mg deficiency. However, few experimental studies have been undertaken on Mg-deficiency-induced behavioural changes. Even fewer studies have been carried out on acute behavioural responses to clonidine, D-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan (HTP), which might characterize possible neuromediator changes in Mg deficiency. The effects of correcting Mg deficiency by magnesium chloride (MgCl2 · 6H2O) and the combination of this salt with vitamin B6, on the behavioural manifestations of Mg deficiency have never been described as well. OBJECTIVE: The aims of this study were: to estimate effect of MgCl2 · 6H2O alone and in combination with vitamin B6 on acute behavioural responses to agonists or blockers of the main neurotransmitter systems in CNS, psychomotor activity and emotional status of rats fed with Mg-deficient diet for 49 days. In our study open field test has shown that in Mg-deficient rats locomotor activity and vertical activity, number of visiting and residence time in central squares were decreased significantly. In the elevated plus maze test, the number of visiting open arms and residence time of rats were significantly less as compared with the control group. In the forced swimming test, time immobile was significantly increased by 44.29% and time of swimming was decreased by 52.79% compared to control. RESULTS: In our study Mg-deficient rats were more sensitive to d-amphetamine-induced motor stereotypes. Mg deficiency antagonized 5-hydroxytryptophan-induced head-twitch response and arecoline-induced tremor. Supplement of MgCl2 · 6H2O with vitamin B6 administered to a Mg-deficient rat increased the Mg level in plasma and erythrocytes. Furthermore, this increase was in relation to vitamin B6 given to the animal. Mg supplementation alone and in combination with pyridoxine normalized acute behavioural responses to d-amphetamine, 5-hydroxytryptophan, and arecoline in Mg deficient rats with a return to pre-deficient levels observed in the Mg sufficient group. DISCUSSION: Combination of Mg salts and pyridoxine hydrochloride can be effective at treating some behavior form of primary Mg deficiency.

Anxiolytic-like effect of Griffonia simplicifolia Baill. seed extract in rats.

The seeds of Griffonia simplicifolia Baill., a tropical shrub native to West Africa, are rich in 5-hydroxy-l-tryptophan (5-HTP), a direct precursor in the synthesis of serotonin (5-HT). In spite of the modern therapeutic application of Griffonia simplicifolia seed extract in mood disorders, no scientific evidence has been provided till now. For this reason the aim of our study was to investigate the effect of Griffonia simplicifolia seed extract on anxiety behavior. Griffonia simplicifolia seed extract, dosed at 1, 5, 10 and 25 mg/kg, was orally administered in rats which were submitted to the dark-light test and open field test, 60 min after the treatment. In the dark-light test, the administration of the extract at the doses of 10 and 25 mg/kg was able to significantly increase the time spent in the light compartment (P<0.05). In the open field test, the extract dosed at 5, 10 and 25 mg/kg induced an anti-tigmotactic effect, as indicated by a significant increase of time spent in the central area of the open field (P<0.01). In conclusion these findings indicate that Griffonia simplicifolia seed extract exerts anxiolytic-like effect in rats and suggest its potential usefulness for the treatment of anxiety in humans.

The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms.

We described the use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms in patients starting a detoxification therapy. Since abstinence from ethanol causes a hypodopaminergic and a hypoopioidergic environment in the reword system circuits, manifesting with withdrawal symptoms, food supplements that contains D-phenylalanine a peptidase inhibitor (of opioide inactivation) and L-amino-acids (for dopamine synthesis) were used to replenish a lack in neurotransmitters and alleviate the symptoms of alcohol withdrawal. 20 patients suffering from alcohol addictions starting a detoxification therapy have been included in a prospective, randomized, double blind study. The patients have been randomly devided in two groups. One group recieved for a period of 40 days a food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan (investigation group), and the control (placebo) group. On the first day of hospitalization the patients performed a SCL-90-R test, and blood samples were taken for measuring liver enzymes, total bilirubin, unbound cortisol and lymphocyte populations. The same was done on the 40th day of hospitalization. During the therapy a significant decrease in SCL-90-R psychiatric symptoms scores and a significant increase in CD4 lymphocyte count was observed in the investigation group. The cortisol values were significantly, but equally decreased in both groups, the same was with the liver enzymes and the total bilirubin values. We conclude that abstinence causes a major stress for the patients. The use of food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect the serum cortisol levels, which are probably more affected by liver inflammation and the liver restitution.

Oral administration of 5-hydroxytryptophan (5-HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task.

OBJECTIVE: Although the serotonin precursor 5-hydroxytryptophan (5-HTP) is marketed as a psychoactive nutritional supplement, knowledge is limited regarding the effects of exogenous 5-HTP on brain activity. This study examined if oral administration of 5-HTP to healthy adults impacted: (1) mood states, as measured by the Profile of Mood States (POMS); and (2) performance on the Iowa Gambling Task (IGT), a measure sensitive to alterations in frontocortical serotonin levels. METHODS: A sample of 46 undergraduates participated, and each received either two 50 mg 5-HTP capsules or placebos, and completed the IGT and POMS following an absorption period. RESULTS: 5-HTP did not significantly alter mood states, but did impair performance on the IGT. Specifically, the 5-HTP group performed more poorly than the placebo group during the first 20 trials of the IGT but did not differ from the placebo group on trials 21-100. This suggests that oral 5-HTP specifically impaired decision making under ambiguity but not under risk. Males also performed more poorly on the first 20 trials of the IGT, regardless of treatment group. CONCLUSIONS: Oral 5-HTP is psychoactive at low doses. Decisions made under ambiguity may be differentially sensitive to increased serotonin release or associated reductions in frontocortical dopamine activity.

Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation.

OBJECTIVE: To test the effect on satiety of a formulation comprising plant extracts naturally containing 5-hydroxytryptophan, delivered as sublingual spray (5HTP-Nat Exts), administered five times a day for 2 months. DESIGN: Two-month, randomized, double-blind, placebo-controlled trial. SUBJECTS: A total of 27 healthy, adult overweight women were randomly assigned to the treatment (14) or the placebo group (13). MEASUREMENTS: Visual analog scales were used to assess appetite sensations every day. Moreover, the study evaluated the bioavailability of 5-hydroxytryptophan following sublingual delivery over 8 weeks, by comparing 24-h urinary excretion of 5-hydroxy-3-indoleacetic acid (5-HIAA), determined at baseline and after 2 months. Other secondary end points of the study were to compare body composition, depressive symptoms, severity of binge eating and quality of life. Finally, the study tested whether a single administration of 5HTP-Nat Exts in fasting state has an effect on amino-acid profile and on appetite ratings and whether 5HTP-Nat Exts administered before a fixed test meal has any effect on satiety. RESULTS: The group using the 5HTP-Nat Exts experienced a significantly greater increase in their sensation of satiety over an 8-week timeframe and in fasting state following administration of 5HTP-Nat Exts than the placebo group did (AUC=305.2 (52.8) vs 236.6 (59.4), mean difference -68.7 (95% confidence interval (CI) -116.2 to -21.2), P=0.007; mean difference in Haber score change 2.5 (95% CI 0.62-3.12, P=0.007)). A difference was observed between the groups for the mean change in 5-HIAA. All the amino acids evaluated after a single administration of 5HTP-Nat Exts were found to be similar. Differences were found for the mean change in body mass index, skinfold thicknesses and hip circumference. The other parameters were found to be similar. CONCLUSION: All these findings suggest that 5HTP-Nat Exts may be safely used to treat the problem of appetite control in overweight women during a weight loss program.

Serum corticosterone increases reflect enhanced uptake inhibitor-induced elevation of extracellular 5-hydroxytryptamine in rat hypothalamus.

The increase in extracellular 5-hydroxytryptamine (5-HT) in rat hypothalamus following administration of fluoxetine, a 5-HT-uptake inhibitor, was enhanced by the injection of LY206130(1-[1-H-indol-4-yloxy]-3-[cyclohexylamino]-2-prop ano l maleate), a 5HT1A receptor antagonist, or by L-5-hydroxytryptophan (L-5-HTP), the 5-HT precursor. Elevation of serum corticosterone, measured as a functional output of hypothalamic 5-HT pathways, was greater in rats treated with fluoxetine plus LY206130 or with fluoxetine plus L-5-HTP than in rats treated with the agents alone. Synergism between effects of fluoxetine and L-5HTP has often been reported, but this is the first report of an increased functional effect when a 5-HT1A receptor antagonist is combined with a 5-HT uptake inhibitor to augment the increase in extracellular 5-HT.

Effect of some chemical radioprotectors on mouse bone marrow.

Effect of HT, AET and Se on mice bone marrow has been studied by counting bone marrow micronucleated cells and endogenous spleen colony count (CFU-S). Combination of HT and AET used as a radioprotector has not caused any significant variation in any of the parameter studied when administered once, it increases bone marrow micronucleated cells and decreases CFU-S slightly after daily administration for 7 days. The individual constituent of the combination administered singly does not increase micronucleated cell number. Seven consecutive doses of HT + AET and same in combination with Se enhances micronucleated cells to a higher level. Daily injection of Se alone up to 7 days also causes an increase in micronucleated cells upto same level. CFU-S pool does not show any significant change in number of bone marrow cells through out the study except in the groups where animals were treated with Se.

Radioprotection of spleen by a combination of 5-hydroxy-L-tryptophan and 2-aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats.

Radioprotective efficiency of the combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) with 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg) in protecting splenic tissue following 8 Gy whole-body gamma radiation (WBGR) has been studied in adult male Sprague Dawley rats. Loss in splenic weight, splenic cells and DNA was observed following & Gy WBGR, which was modified significantly in 5-HTP+AET (ip) pretreated group. The study further showed that pre-treatment with this formulation led to an increased superoxide dismutase (SOD) activity and a decrease in lactate/pyruvate ratio in the cytosol fraction of the spleen.

Thermogenic actions of tryptophan in the rat are mediated independently of 5-HT.

Serotonin (5-HT) has been implicated in the central control of energy balance, via inhibition of food intake and stimulation of thermogenesis. Its rate of synthesis in brain is dependent on the availability of its precursor amino acid, tryptophan. The objective of the present study was therefore to investigate the thermogenic actions of tryptophan and to determine whether these actions are mediated by 5-HT. Central or peripheral injections of 5-HT (i.c.v.; 0.5-40 micrograms), 5-hydroxytryptophan (5-HTP) (i.c.v.; 20 micrograms) or tryptophan (i.p.; 20 mg/kg, i.c.v.; 12-60 micrograms) significantly increased resting oxygen consumption (VO2 by approximately 15-20%) in conscious rats, without apparent effects on physical activity. Small increases (5-7%) in VO2 were also observed following peripheral injections of aspartate or glycine (20 mg/kg) but not taurine, whilst central injections of tyrosine or leucine (15-18 micrograms) significantly increased VO2 by 15%. We have previously reported that the thermogenic and anorexic actions of 5-HT are mediated by corticotropin-releasing factor (CRF). In the present study, the thermogenic actions of 5-HTP, like those of 5-HT, were significantly reduced by pretreatment (5 min before) with the CRF antagonist alpha-helical CRF9-41 (25 micrograms, i.c.v.) or a polyclonal antibody to CRF. However, the thermogenic actions of tryptophan were not significantly modified by pretreatment with either the 5-HT antagonist, methysergide (20 micrograms, i.c.v.) or with the CRF antagonist or antibody and thus appear to act through different mechanisms to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of central 5-hydroxytryptamine in acupuncture analgesia.

The role played by central 5-hydroxytryptamine (5-HT) in acupuncture analgesia (AA) has been studied in rats with the tail-flick response as the antinociceptive test. The analgesic effect of acupuncture can be enhanced or lowered by the increment or the decrement of the 5-HT level in the CNS. Furthermore, the turnover rate of 5-HT in the CNS has been found to be greatly facilitated during the period of acupuncture. The results imply that 5-HT in the CNS may be one of the most important neurochemical agents mediating AA.

Effect of hypothalamic surgery on prolactin release induced by 5-hydroxytryptophan (5-HTP) in rats.

Intravenous injections of varying doses of 5-HTP (1, 3 and 5 mg/100 g body wt), a precursor of serotonin, caused a significant and dose-related increase in plasma prolactin concentrations in urethane-anesthetized rats. Increases in plasma prolactin concentrations caused by 5-HTP (1 mg/100 g body wt iv) were abolished by the concomitant administration of L-DOPA (2 mg/100 g body wt iv). Plasma prolactin levels were also significantly elevated following the injection of 5-HTP in rats with complete hypothalamic deafferentation, whereas 5-HTP had no significant effect on plasma prolactin levels in rats with extensive hypothalamic ablation. These results suggest that 5-HTP causes prolactin secretion by stimulating the serotoninergic mechanism in the hypothalamus.