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In teleosts, peripheral serotonin (5-HT) and melatonin (MEL) are synthesised in the gastrointestinal tract (GIT) and regulate secretion and motility processes. Their production is regulated by diet and the passage of food through the GIT. This study aimed to evaluate how intestinal 5-HT, melatonin, and the activity of digestive enzymes varied with food passage time through GIT in Atlantic salmon (Salmo salar). We fed fish diets supplemented with tryptophan and melatonin (L-Trp 2.5% and MEL 0.01%) and measured the activity of digestive enzymes (amylase, lipase, and total protease) in the pyloric caeca, midgut, and hindgut at different times after feeding. 5-HT levels increased in all GIT portions and diets at 120 min post-intake and were highest in the pyloric caeca. Intestinal enzymatic activity was varied with diet, post-intake time and in different intestinal portions. In conclusion, food passage time directly affects GIT 5-HT secretion and digestive enzyme activity in S. salar, and diet composition regulates S. salar GIT function., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Like many wild species, the European hamster (Cricetus cricetus) adapts to the marked seasonal changes in its environment, namely by hibernation and inhibition of sexual activity in winter. These annual functions are driven by the variation in the environmental factors (light, temperature) that are transmitted to the body through large variations in the duration and amplitude of the nocturnal melatonin rhythm. Here we report that the seasonal variation in melatonin synthesis is mainly driven by arylalkylamine N-acetyltransferase gene transcription and enzyme activation. This, however, does not exclude participation of hydroxyindole-O-methyltransferase, which may relay environmental temperature information. The in vivo experiments show that norepinephrine stimulates melatonin synthesis, this effect being gated at night. The possibility that the variation in pineal metabolism depends on a seasonal change in the suprachiasmatic nuclei clock circadian activity that is transmitted by norepinephrine is discussed.

The present paper discusses the effect of a single melatonin treatment (0.5 mg/kg, i.p.) on the dopaminergic metabolism in the hypothalamus and pituitary of the rainbow trout. The effects of exogenous melatonin on dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents were compared with the variations in the content of these catecholamines associated to the natural increase in the endogenous melatonin from daytime (3 hr before lights off) to nighttime (3 hr after lights off). Animals treated with melatonin showed a rapid (maximal values at 30 min post-injection) and relatively sustained rise in plasma melatonin levels, which reached supraphysiological ranges. The increase in circulating melatonin was accompanied by a reduction in the amount of DOPAC in both the hypothalamus (30, 60, and 120 min after i.p. melatonin) and the pituitary (120 min after i.p. melatonin) as well as in the pituitary DOPAC/DA ratio (60 and 120 min after i.p. melatonin). Similarly, the increase in circulating melatonin levels from the daytime to nighttime was associated with decreases in the contents of DOPAC in both the hypothalamus and pituitary and in the DOPAC/DA ratio in the pituitary. These data suggest that the inhibition of the hypothalamic-pituitary dopaminergic metabolism may be a specific mechanism of melatonin action in the trout brain that might operate following changes in the secretion of the hormone from the pineal gland.

Melatonin content and release from Harderian glands (HGs) has been measured by an in vitro perifusion technique in three rodent species: Wistar rat, Syrian hamster, and Siberian hamster. Melatonin immunoreactive concentrations in HGs of animals killed at 10.00 hr were 0.31 +/- 0.031 pg/mg gland in male Wistar rat, 0.54 +/- 0.026 pg/mg gland in male Siberian hamster, 0.17 +/- 0.070 and 0.20 +/- 0.059 pg/mg gland in male and female Syrian hamster, respectively. In all species examined, isolated HGs perifused for 9-15 hr released melatonin but did not stabilize their melatonin release rate. No sex-related difference could be noted in the HG melatonin release rate. The total amount of melatonin released over a 15 hr long perifusion was about 0.075 +/- 0.004 ng/15 h/mg gland and 0.063 +/- 0.010 ng/15 hr/mg gland in male and female Wistar rat, respectively; 0.155 +/- 0.019 ng/15 hr/mg gland and 0.141 +/- 0.006 ng/15 hr/mg gland in male and female Siberian hamster, respectively; 0.035 +/- 0.003 ng/15 hr/mg gland and 0.045 +/- 0.004 ng/15 hr/mg gland in male and female Syrian hamster, respectively. This amount, which is higher than the tissue levels, demonstrates the de novo melatonin synthesis. This is confirmed by the fact that infusion of the indoleamine precursor, tryptophan (TRP), stimulated melatonin secretion from HGs. The melatonin release is increased by 2.5-fold in male and female Wistar rat, 1.5-fold in male and female Siberian hamster, and 2.0- and 3.0-fold in male and female Syrian hamster, respectively. Treatment with a TRP hydroxylase inhibitor, para-chlorophenylalanine, reduced basal melatonin release and inhibited the TRP-induced melatonin stimulation. Kinetics and amounts of melatonin released were not affected by pinealectomy, ruling out a possible plasmatic origin of the HG melatonin. Isoproterenol, a beta-adrenergic agonist, and dibutyryl cyclic AMP, a cyclic AMP analogue, failed to stimulate HG melatonin secretion. In conclusion, these results confirm the presence of melatonin in the HGs and demonstrate that melatonin is synthesized in and released from isolated rodent HGs.

This study investigated whether the activation of pinealocyte beta-adrenergic receptors is involved in the regulation of serotonin (5-HT) synthesis and release, as it is for melatonin production. In addition, the role of the intra- and extra-cellular 5-HT in modulating the synthesis of melatonin induced by the beta-adrenergic agonist isoproterenol (ISO) was also studied. The incubation of dissociated pinealocytes with 0.1-10 microM ISO resulted in a concentration-dependent increase of melatonin synthesis. 5-HT release and intracellular 5-HT content were increased by 0.1 and 1 microM ISO but they were reduced after ISO 10 microM. Moreover, when incubated with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA), the secretion of 5-HT as well as the intracellular 5-HT levels were markedly reduced in both ISO-stimulated and unstimulated conditions. Melatonin release was also inhibited by PCPA, although it responded in the expected manner to increasing concentrations of ISO. These data indicate that the release of 5-HT from pinealocytes depends on the availability of cytoplasmic 5-HT, which in turn is highly dependent on the tryptophan hydroxylase activity. In cells stimulated with moderate ISO concentrations, 5-HT release may be an important regulatory process of pineal 5-HT. After a large stimulation of N-acetyltransferase (NAT) activity by ISO, the synthesis of melatonin prevails on 5-HT release, whose decrease is associated to a deficit of intracellular 5-HT. On the other hand, the present study shows that the incubation of pineal cells with high concentrations of 5-HT or with a selective 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine, reverses partially the inhibitory effect of PCPA on the ISO-stimulated melatonin synthesis. In contrast the 5-HT2 antagonist, ketanserin, results in an inhibiton of the release of melatonin following ISO stimulation. These results suggest that released 5-HT may have a role in the full expression of the beta-adrenergically induced NAT activity and, thus, may contribute to the optimal melatonin synthesis at night.

The influence of the pineal gland on the hypothalamic serotonergic function was examined by studying the effects of long-term pinealectomy (1 month) and melatonin replacement (500 micrograms/kg; 10 days) on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content as well as on the in vivo 5-HT synthesis rate in discrete hypothalamic nuclei. Pinealectomy was followed by a significant decrease of 5-HT content in the anterior hypothalamic nuclei (AHN) and the ventromedial hypothalamic nuclei (VMHN), and also in 5-HIAA content in lateral (LPON) and medial preoptic nuclei (MPON). The 5-HT synthesis rate, estimated from the accumulation of 5-hydroxytryptophan after blockade of the 1-amino acid decarboxylase activity, were also decreased in the AHN and the paraventricular hypothalamic nuclei (PVHN) of pinealectomized rats. In contrast, an enhanced 5-HT synthesis rate and basal 5-HIAA content were found in the suprachiasmatic nuclei (SCN) after pinealectomy. Daily treatment with melatonin for 10 days reversed most of the effects induced by pinealectomy. Thus, melatonin increased the levels of 5-HT in the AHN and VMHN, and slightly increased the 5-HIAA content in preoptic nuclei. In addition, melatonin increased the 5-HT synthesis rate in the AHN and VMHN, but also in the MPON, VMHN and dorsomedial hypothalamic nuclei (DMHN) where pinealectomy had no effect. By contrast, melatonin treatment did not affect SCN 5-HT synthesis rate, although it decreased 5-HIAA levels. The results demonstrate that melatonin is able to stimulate 5-HT metabolism in most of the hypothalamic areas, but inhibits SCN 5-HT function. Some of the effects of melatonin seems to be exerted by modulating the synthesis of the amine, although melatonin likely also interacts with other regulatory processes of 5-HT function (i.e. release/uptake). The well defined presence of melatonin receptors in the rat SCN, and its absence in other hypothalamic structures, suggest that this may be the mechanism mediating the differential response to endogenous melatonin. Moreover, the larger effect of exogenous melatonin in relation to pinealectomy suggests the presence of melatonin unespecific effects possibly owing to supraphysiological doses. The present findings may be relevant for the mode of action of melatonin and its implication in several endocrine and behavioral functions mediated by serotonergic neurons.

This study examined the effects induced by long-term pinealectomy, daily melatonin treatment to pinealectomized and intact rats, and a single melatonin injection on [14C]-serotonin (5-HT) uptake and release from synaptosomes obtained of hypothalamic regions. Pinealectomy inhibited the accumulation of labeled 5-HT by synaptosomes of the preoptic area-anterior hypothalamus (POA-AH), but it failed to alter the [K+]-evoked 5-HT release. Melatonin treatment for 10 consecutive days to pinealectomized rats restored 5-HT uptake in POA-AH, and also increased 5-HT release in medial and posterior hypothalamus. These results suggest that pineal melatonin plays a stimulatory role on the serotoninergic terminals of the hypothalamus. Moreover, when daily melatonin treatment was administered to intact rats a significant increase in 5-HT uptake activity by synaptosomes of all the hypothalamic regions was observed, but 5-HT release was unaffected. In contrast, a single melatonin injection induced a significant decrease in 5-HT release from synaptosomes of the POA-AH was observed. The results suggest the existence of a differential sensitivity in the mechanisms mediating melatonin actions on 5-HT uptake/release, which depends on the presence of the pineal gland in the animals and on the frequency of the treatments with the pineal hormone.

The acute effects of two doses (0.5 and 1 mg/kg) of melatonin on the levels of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in several rat brain regions were studied. Tryptophan content in the brain regions was unchanged by the treatments. Melatonin at a dosage of 0.5 mg/kg increased medial hypothalamic serotonin levels at 60 and 90 min after the injection. However, the dose of 1 mg/kg increased the levels of this amine or its metabolite in the preoptic area-anterior hypothalamus, medial and posterior hypothalamus, amygdala, and midbrain. These results suggest a specific regional sensitivity to melatonin as well as a dose-dependent response. The stimulatory melatonin effect on the serotoninergic system was also observed after a daily treatment with this hormone (0.5 mg/kg, twice daily during 10 days) in both intact or pinealectomized rats. In intact rats, melatonin treatment increased the levels of 5-hydroxyindole-3-acetic acid in the preoptic area-anterior hypothalamus and medial hypothalamus, while in pinealectomized rats melatonin increased the serotonin content in the medial hypothalamic region. The data support the idea that melatonin has a selective action on serotonin metabolism in regions that contain serotoninergic terminals, especially at medial hypothalamic level.