Circadian Levels of Serotonin in Plasma and Brain after Oral Administration of Tryptophan in Rats

Abstract

Serotonin, one of the most important neurotransmitters in the central nervous system, is synthesized by the amino acid, tryptophan. Given that this essential amino acid is consumed in the diet, the aim of this study was to evaluate the effect of orally administered L-tryptophan (125 mg/kg) on circadian variations in the levels of serotonin in brain and plasma. We used male Wistar rats of 14 ± 2 weeks of age (n = 240), maintained under conditions of a 12-hr light:dark cycle, and food and water ad libitum . Tryptophan administration was by gavage in a daily single dose at 7 p.m. for 7 days. The serotonin levels were measured by ELISA every hour at night (8 p.m. to 8 a.m.) and every 4 hr during daytime (8 a.m. to 8 p.m.). The results show that in both the tryptophan-treated and untreated groups the highest values appeared during the beginning of the darkness with a peak at 9, 10 and 11 p.m. in controls, and at 9 p.m. in the tryptophan-treated group. After tryptophan administration, the levels of serotonin were significantly higher in the plasma and all the brain regions analysed than in the control group. This increase of serotonin levels was greater in the pineal gland than in other brain regions, and the least in plasma. In conclusion, oral administration of tryptophan during 7 days enhances serotonin levels over a 24-hr period, and produces an advance in the peak of serotonin in both plasma and different brain regions.Circadian rhythms are generated and maintained by the biological clock located in the suprachiasmatic nucleus [1,2]. Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter strongly implicated in the regulation of these rhythms [3]. It is also involved in many functions throughout the brain, playing an important role in behaviour, depression, mood regulation, cognitive function, anxiety, sleep, appetite, sexual function, blood flow to the brain [4], and also has a fundamental role of precursor in melatonin synthesis.The synthesis and release of 5-HT are subject to circadian variations. Barassin et al . [5] and Dudley et al . [6] described in suprachiasmatic nucleus of rats and hamsters, respectively, that the maximum levels in release of 5-HT were obtained at the light/dark transition, just at the beginning of the dark phase, after which output of 5-HT decreased to basal levels throughout the remainder of the night. In previous research [7], we noted in rats that the peaks of 5-HT in basal conditions in plasma and different brain regions (pineal gland, hypothalamus, hippocampus, cerebellum and striatum) appear at the beginning of the dark period. This pattern can be altered in vitro by the use of 5-HT agonists acting at the level of the 5-HT1A receptors, with advance of the diurnal phase and delay of the nocturnal phase [8]. It has been found not only that this pattern of production of 5-HT persists in conditions of constant darkness [9][10][11], but also that it is influenced by luminosity signals [11,12]. Both the synthesis and the diurnal release of this neurotransmitte...

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Plasma concentration of tryptophan and pregnancy-induced hypertension

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