Tryptophan increases nocturnal rest and affects melatonin and serotonin serum levels in old ringdove

Abstract

The sleep promoting functions of melatonin have gained wide scientific attention due to the ability of this indole to provide relief from sleep inefficiency and the temporal relationship between its nocturnal rise in the blood and the “opening of the sleep gate” at night. However, little is known about the effects exerted by its precursor, the amino acid tryptophan. We studied the effect of a 7-day administration of two concentrations of tryptophan (125 and 300 kg b.w.) on the activity/rest rhythms of ringdove, aged 2–3 (young) and 10–12 (old) years, and on the serum levels of serotonin and melatonin. Activity pulses were logged before, during, and up to 5 days after the treatments. The animals received 125 or 300 mg/kg b.w. per animal/day at 09:00 h or at 19:00 h. Subsequently we chose the treatment which gave the best results in terms of nocturnal rest without affecting diurnal activity, i.e., 300 mg/kg b.w. administered to old animals at 09:00 h, 1 h after lights on, for the serotonin and melatonin measurements. During this treatment, the nocturnal and diurnal levels and amplitudes of serotonin and melatonin were all significantly higher than the corresponding levels before and after the treatment. In sum, our results point to an improvement of nocturnal rest in this animal model of old ringdove when administering 300 mg/kg tryptophan 1 h after lights on.

Introduction

Evidence from naturalistic observations supports the suggestion that the endogenous role of melatonin may be to enhance behaviour normally associated with night in both diurnal and nocturnal species, i.e., melatonin can be viewed as a neuroendocrine transducer promoting an increased propensity for “dark appropriate” behaviour [1]. The endogenous melatonin rhythm exhibits a close association with the endogenous circadian component of the sleep propensity rhythm. This has led to the idea that melatonin is an internal sleep “facilitator” in diurnally-active animals, and therefore useful in the treatment of insomnia and the readjustment of circadian rhythms [2]. Successful use of melatonin's chronobiotic properties has been reported in other sleep disorders associated with abnormal timing of the circadian system: jetlag, shiftwork, delayed sleep phase syndrome, and some sleep problems of the elderly [3]. The related indolamine, 5-HT, is known to increase the proportion of slow wave sleep [4], as well as being a waking neurotransmitter [5]. Also, the close relationship between serotonergic activity and the adjustments of circadian phase suggest that 5-HT also plays a role in the endogenous regulation of the circadian clock [6].

Despite the major role that melatonin and 5-HT play in sleep, little is known about the effect of tryptophan, the common precursor in their biosynthesis. Tryptophan administered in the diet is known to increase the availability of 5-HT in the brain, the EEG delta potential, and the amount of NREM [7]. It has also been observed in mammals that orally ingested tryptophan increases the brain levels of 5-HT during the day and the circulating levels of melatonin during the immediately following night [8], and recently it has been shown in our animal model that this amino acid significantly increases the hippocampus, striatum, and hypothalamus 5-HT contents [9], and reduces the expression of c-fos in the suprachiasmatic nucleus [10] whose levels are high in several cerebral regions during spontaneous waking or sleep deprivation and fall after a few hours of sleep [11].

The aim of the present work was to investigate the effect on rest/activity of oral administration of tryptophan to both young and old diurnal monophasic animals (ringdove, Streptopelia risoria). Once the concentration of tryptophan that was most effective in improving nocturnal rest without affecting diurnal activity had been established, the effects of these treatments on the serum 5-HT and melatonin levels were studied.