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Over the last few years, an increasing interest in the scientific research of natural antioxidant molecules from plants capable to attenuate, or even prevent, stress oxidative-related disorders, such as diabetes, inflammatory, and neurological pathologies has been observed. Serotonin and melatonin are two of these molecules, being widely found in Mediterranean foodstuffs, fruits, vegetables, and medicinal herbs. The consumption of foods containing both antioxidants can raise their physiologic concentrations in blood and, consequently, enhance antioxidant defenses, improve mood, and treat sleep disorders, depression, and anxiety. Currently, there exist several analytical methods suitable for the determination of melatonin and serotonin in fruits and edible plants. Among them, the most used include chromatographic techniques and immunological assays. This work aims to present a comprehensive overview of the biosynthesis of these indolamines in nature, the most common techniques used to detect and quantify both compounds in fruits, vegetables, medicinal herbs, and other food sources, as well as to address their health benefits, particularly their antioxidant, neuroprotective, and sleep-promoting effects.

The article presents the results of the study on morphological rearrangements of structural changes in the rat pineal gland under the influence of heavy metal salts and correction with L-tocopherol during 30 days. General morphological and statistical research methods were used (histological, morphometric and statistic methods). The protective effect of L-tocopherol caused in the pineal gland a number of compensatory-adaptive processes aimed at neutralizing the stressor’s impact on the organ. The 30- days protective period of L-tocopherol is insufficient to completely neutralize the impact of heavy metals on the organ: the glial response was activated, vascular area increased, vascular wall permeability was impaired, edema was formed and the connective tissue component growth was taking place, indicating dysfunctional reorganization in the gland’s secretory activity. The above morphological changes negatively affected the processes of hormones evacuation into the blood, the course of the general adaptation syndrome and the homeostasis restoration in the organ. У статті представлені результати дослідження морфологічних перебудов структурних змін в епіфізі щурів під впливом солей важких металів та корекції L-токоферолом на протязі 30 днів. Використовувались загальні морфологічні та статистичні методи дослідження (гістологічні, морфометричні та статистичні). Захисна дія L-токоферолу викликала в епіфізі ряд компенсаторно-адаптаційних процесів, спрямованих на нейтралізацію впливу стресора на орган. Але, 30- денного захисного періоду L-токоферолу недостатньо, щоб повністю нейтралізувати вплив важких металів на орган: активувалася гліальна реакція, збільшувалася площа судин, погіршувалася проникність судинної стінки, формувався набряк і зростала сполучнотканинна складова частина залози, що свідчить про дисфункціональну перебудову секреторної діяльності органу. Вищевказані морфологічні зміни негативно вплинули на процеси евакуації гормонів у кров, перебіг загального адаптаційного синдрому та відновлення гомеостазу у органі. The work is a fragment of the research project “Morphofunctional aspects of homeostasis”, state registration No. 0118U006611and a fragment of the research project “Modern views on the morphogenesis of general pathological processes”, state registration No. 0119U100887.

Early diagnosis of Parkinson’s disease (PD) remains a challenge to date. New evidence highlights the potential clinical value of circulating trace amines (TAs) in early-stage PD and their involvement in disease progression. A new ultra performance chromatography mass spectrometry (UPLC-MS/MS) method was developed to quantify plasmatic TAs, and the catecholamines and indolamines pertaining to the same biochemical pathways. Three groups of subjects were recruited: 21 de novo, drug untreated, PD patients, 27 in treatment PD patients and 10 healthy subjects as controls. Multivariate and univariate data analyses were applied to reveal metabolic changes among the groups in attempt to discover new putative markers for early PD detection and disease progression. Different circulating levels of tyrosine (p = 0.002), tyramine (p 0.75). The findings of this pilot cross-sectional study suggest that biochemical anomalies of the aminergic and indolic neurotransmitters occur in PD patients. Compounds within the TAs family may constitute putative markers for early stage detection and progression of PD.

Indolamines are tryptophan-derived specialized metabolites that belong to the huge and ubiquitous indole alkaloids group. Serotonin and melatonin are the best-characterized members of this family, given their many hormonal and physiological roles in animals. Following their discovery in several plant families, the study of plant indolamines has flourished over the last few decades and their involvement in many important processes has been proposed, including stress responses, growth and development, and reproduction, leading to their classification by some authors as a new category of phytohormones. However, the complex puzzle of the indolamines is far from resolved, particularly the biological roles of tryptamine, the early tryptophan-derived serotonin precursor representing the central hub of downstream plant indolamines and many specialized indole alkaloids. Tryptophan decarboxylase, which catalyzes the synthesis of tryptamine, appears to strictly regulate the flux of carbon and nitrogen from the tryptophan pool into the indolamine pathway. Furthermore, tryptamine accumulates to high levels in the reproductive organs of many plant species, and therefore cannot be classed as a mere intermediate but rather as an end product with potentially important functions in fruits and seeds. This review summarizes current knowledge on the role of tryptamine and its close relative serotonin, emphasizing the need for a clear understanding of the functions of, and mutual relations between, these two indolamines and their biosynthesis pathways in plants.

Bipyridinium salts, commonly known as viologens, are &pi, acceptor molecules that strongly interact with &pi, donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of &pi, donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1&middot, 4PF6&ndash, 4&middot, 4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of &pi, donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1&middot, 4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

Serotonin (5-HT) is member of a family of indolamine molecules that participate in a wide variety of biological processes. Despite its important role in the regulation of local blood systems, little is known about the physiological function of 5-HT in reproductive organs, its functional implications, and its role in the reproduction of mammals. In the present work, we evaluated the localization and distribution of 5-HT (using histochemical analysis of indolamines) and different components of the serotoninergic system in rat testes. We detected local synthesis and degradation through immunofluorescence and western blot analyses against the TPH1, MAOA, 5-HTT, and VMAT1 serotonin transporters. We also identified the localization and distribution of the 5-HT1B, 5-HT2A, and 5-HT3Areceptors. RT-PCR results showed the presence of the Tph1, Maoa, Slc6a4, and Htr3a genes in testes and in the brain stem (Tph1 was used as a negative control). High-performance liquid chromatography was used to determine the presence of 5-HT and the activity of tryptophan hydroxylase in testes homogenatesin vitro. Our observations suggest that TPH1 activity and local 5-HT synthesis befall in rat testes. We propose that 5-HT could participate in the regulation of testosterone synthesis and in the spermatogenesis process via local serotoninergic system. However, more studies are needed before concluding that rat testes, or those of other mammals, contain an active form of tryptophan hydroxylase and produce 5-HT.

The hydroxyl radical (•OH) scavenging activities of Melatonin, an endogenously produced neurohormone and its related indolamines like N-acetyl tryptophan (NAT) and N-acetyl serotonin (NAS) have been investigated using density functional theory. The mechanism involves 4 steps: initial radical addition to position-3 of the indole ring, keto-amine to enol-imine tautomerization, cyclisation, and finally, addition of a second •OH leading to a cyclic end product. Incorporation of an explicit water molecule in tautomerization step leads to a significant reduction in the barrier of this step, so that the subsequent cyclisation step becomes rate-limiting. In agreement with the very high reactivity of •OH, the initial and final addition of •OH to indolamine are found to be barrierless. Radical adduct formed in the initial step was found to be very stable due to the extensive conjugation present in the substrate. Our calculations show that melatonin is the most effective radical scavenger among the three molecules chosen. NAS was found to exhibit antiradical property comparable to that of melatonin. In contrast to the general observation of reduced antioxidant activity of tryptophan, a non-natural derivative of tryptophan used here (NAT) is found to have good radical scavenging activity. This work further implies that non-natural derivatives of indolamines might as well be useful in the detoxification of free radicals as they exhibit almost comparable antioxidant efficiency as that of melatonin.

Kiwifruit (Actinidia deliciosa cv. Hayward) is a commercially important crop with highly nutritional green fleshy fruits. The post-harvest maturation of the fruits is well characterized, but little is known about the metabolic changes that occur during fruit development. Here we used untargeted metabolomics to characterize the non-volatile metabolite profile of kiwifruits collected at different time points after anthesis, revealing profound metabolic changes before the onset of ripening including the depletion of many classes of phenolic compounds. In contrast, the phytohormone abscisic acid accumulated during development and ripening, along with two indolamines (serotonin and its precursor tryptamine), and these were monitored in greater detail by targeted metabolomics. The role of indolamines in kiwifruit development is completely unknown, so we also characterized the identity of genes encoding tryptophan decarboxylase in A. deliciosa and its close relative A. chinensis to provide insight into the corresponding biological processes. Our results indicate that abscisic acid and indolamines fulfill unrecognized functions in the development and ripening of kiwifruits.

Ruthenium polypyridine complexes have proved to be useful caging groups for visible-light photodelivery of biomolecules. In most photoreactions, one ligand is expelled upon irradiation, yielding ruthenium mono-aqua complexes and no other photoproduct. In this work we show that a long-lived transient photoproduct is generated when the ruthenium complexes involve indolamines. The spatial conformation of this species is compatible with a cyclic structure that contains both the amine and the normally non-coordinating aromatic ring coordinated to the ruthenium center. Fil: Carrone, Guillermo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Zayat, Leonardo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Slep, Leonardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Etchenique, Roberto Argentino. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina

Since its discovery in the past century by Green, Page and Rapport (1948), to the present time, several physiological actions of serotonin has been discovered. Besides physiological functions, several components of serotoninergic system and its participation in some neurological diseases (i.e. depression, schizophrenia) also have been reported. During previous decades, a lot of experimental techniques have allowed us to locate, detect, analyze and describe the serotoninergic system and its role in different organs and tissues; at the time of 60’s and 70’s of century XX, techniques such as histochemistry for indolamines or Falck-Hillarp method, fluorescence microscopy and the realization of measurements of concentrations in tissues or blood using chromatography enabled significant progress in the study of this indolamine

We investigated innervation to body wall muscles as well as distribution of 5-HT (serotonin) and its effects on longitudinal muscles of body wall (LMBW) of the sea cucumber Apostichopus japonicus. With serial sections we found neural branches and fibers extending from hyponeural part of radial nerve towards LMBW and circular muscles of body wall. With the aqueous aldehyde (Faglu) method yellow fluorescence indicating indolamines was observed in LMBW and in the mesentery connecting LMBW to the body wall. With indirect immunohistochemistry 5-HT-like immunoreactivity was observed in LMBW and in mesentery. These results strongly suggested that both LMBW and mesentery contained 5-HT. The effects of monoamine neurotransmitters were studied in LMBW. Putative neurotransmitters tested were 5-HT, adrenaline, noradrenaline, dopamine, and DOPA at the concentration of 10(-6) M. The application of 5-HT caused no contraction or relaxation, but it inhibited the contraction induced by 10(-6)-10(-5) M acetylcholine (ACh). Catecholamines were ineffective by themselves and had no effects on the contraction induced by ACh. The present histological, histochemical, and pharmacological studies strongly suggested that holothurian LMBW was innervated by inhibitory serotonergic neurons of the hyponeural nervous system.

[Tyrosine, octopamine, tryptophan, serotonin, putrescine, spermidine, spermine, norepinephrine, epinephrine, and dopamine were measured by means of high performance liquid chromatography (HPLC) in gills (anterior and posterior) and haemolymph extracts of the freshwater Chinese mitten crab, Eriocheir sinensis. These results may be considered as basic data to be used as control physiological doses, to which to refer for injection or for in vitro perfusion experiments. No significant difference has been detected between anterior respiratory and posterior salttransporting gills. After 10 days acclimation to sea water, a significant increase of haemolymph norepinephrine and dopamine has been observed. Exposure to hydrostatic pressure (101 ATA for 5 hours) also results in an octopamine increase in the haemolymph. In addition, there is a tryptophan increase in both the anterior and the posterior gills. Results are discussed in terms of possible correlations of the concentrations of polyamines, indoleamines, and catecholamines with osmoregulation and behaviour. Les concentrations en tyrosine, octopamine, tryptophane, serotonine, putrescine, spermidine, spermine, norepinephrine, epinephrine et dopamine d'extraits branchiaux (branchies anterieures et posterieures) et hemolymphatiques ont ete mesurees en chromatographie liquide a haute performance chez le crabe chinois Eriocheir sinensis d'eau douce dans le but, notamment, de disposer de valeurs de reference a utiliser comme niveaux physiologiques controles auxquels se referer lors d'experiences d'injection ou de perfusions in vitro. Aucune difference significative n'a ete detectee entre les branchies anterieures "respiratoires" et les branchies posterieures "transportrices de sels". A l'issue de 10 jours d'acclimatement a l'eau de mer, on assiste a une augmentation significative de la norepinephrine et de la dopamine hemolymphatiques. De meme, une exposition de 5 heures a 101 ATA de pression hydrostatique aboutit a une augmentation de l'octopamine hemolymphatique. On assiste, par ailleurs aussi, a un accroissement de la concentration en tryptophane dans les deux types de branchies. Les correlations possibles entre les concentrations en polyamines, indolamines, catecholamines ainsi que l'osmoregulation et le comportement sont l'objet d'une discussion approfondie., Tyrosine, octopamine, tryptophan, serotonin, putrescine, spermidine, spermine, norepinephrine, epinephrine, and dopamine were measured by means of high performance liquid chromatography (HPLC) in gills (anterior and posterior) and haemolymph extracts of the freshwater Chinese mitten crab, Eriocheir sinensis. These results may be considered as basic data to be used as control physiological doses, to which to refer for injection or for in vitro perfusion experiments. No significant difference has been detected between anterior respiratory and posterior salttransporting gills. After 10 days acclimation to sea water, a significant increase of haemolymph norepinephrine and dopamine has been observed. Exposure to hydrostatic pressure (101 ATA for 5 hours) also results in an octopamine increase in the haemolymph. In addition, there is a tryptophan increase in both the anterior and the posterior gills. Results are discussed in terms of possible correlations of the concentrations of polyamines, indoleamines, and catecholamines with osmoregulation and behaviour. Les concentrations en tyrosine, octopamine, tryptophane, serotonine, putrescine, spermidine, spermine, norepinephrine, epinephrine et dopamine d'extraits branchiaux (branchies anterieures et posterieures) et hemolymphatiques ont ete mesurees en chromatographie liquide a haute performance chez le crabe chinois Eriocheir sinensis d'eau douce dans le but, notamment, de disposer de valeurs de reference a utiliser comme niveaux physiologiques controles auxquels se referer lors d'experiences d'injection ou de perfusions in vitro. Aucune difference significative n'a ete detectee entre les branchies anterieures "respiratoires" et les branchies posterieures "transportrices de sels". A l'issue de 10 jours d'acclimatement a l'eau de mer, on assiste a une augmentation significative de la norepinephrine et de la dopamine hemolymphatiques. De meme, une exposition de 5 heures a 101 ATA de pression hydrostatique aboutit a une augmentation de l'octopamine hemolymphatique. On assiste, par ailleurs aussi, a un accroissement de la concentration en tryptophane dans les deux types de branchies. Les correlations possibles entre les concentrations en polyamines, indolamines, catecholamines ainsi que l'osmoregulation et le comportement sont l'objet d'une discussion approfondie.]

In an attempt to define the role of the pineal hormone melatonin and two analogues (5-methoxytryptamine, 5MT, and 6-hydroxymelatonin, 6HM) in limiting oxidative stress, the present study investigated the changes in glutathione, lipid peroxidation, and the activity of the antioxidant enzyme glutathione peroxidase after exercise (swimming for 60 min) with or without treatment with the indolamines mentioned. Lipid peroxidation was measured by estimating tissue levels of malondialdehyde and 4-hydroxyalkenals; the experimental animals in these studies were male Sprague-Dawley rats. In the liver, swimming exercise increased the levels of reduced glutathione (GSH) and also significantly increasing oxidized glutathione (GSSG), while decreasing the GSH/GSSG ratio, an index directly related to oxidative stress. When the animals were treated with melatonin, the concentrations of GSH and GSSG were also increased after swimming; however, no reduction in the GSH/GSSG ratio appeared. In the animals treated with 6HM the changes were the same as in those treated with melatonin. In muscle as well, the concentration of GSH and the GSH/GSSG ratio were decreased following 60 min of swimming. Pretreatment of the rats with melatonin prevented these effects. Pretreatment of the rats with both 5MT and 6HM also prevented the changes. Brain GSH/GSSG ratio was not affected by either exercise or indolamine administration. Swimming enhanced lipid peroxidation in the liver, muscle and brain; however, this was prevented in animals treated with melatonin or 6HM before swimming. Glutathione peroxidase was significantly elevated after exercise in the brain but not in the liver and muscle. It is concluded that swimming imposes a severe oxidative stress and suggests that melatonin and, to a lesser degree, 5MT and 6HM confer protection against the oxidative damage associated with swimming for 60 min. This mechanism may be reasonably attributed to their indole structure, which possibly allows these molecules to act as free-radical scavengers.

I. Introduction PAST studies of antidepressants have focused almost exclusively on their effects on the metabolism and receptors of monoamine neurotransmitters in various brain regions. These studies have been extended to the molecular effects of antidepressants and have led to a profoundly expanded understanding of their actions in the central nervous system. For example, long-term administration of antidepressants decreases the expression of tyrosine hydroxylase, down-regulates cAMP-dependent protein kinase, modulates the mRNA expression of central β-adrenoceptors and serotonin (5-HT) receptors, and alters the functional activity of specific G protein subunits and adenylyl cyclase (1). Taken together, these and many other recent observations clearly indicate that antidepressants interfere not only with the production and release of catecholamines and indolamines but also with the signal transduction of those neurotransmitters that have long been implicated in the pathogenesis and treatment of depression...

Neuroendocrine cells are present in virtually all organs of the vertebrate body; however, it is yet uncertain whether they exist in the ovaries. Previous reports of ovarian neurons and neuron-like cells in mammals and birds might have resulted from misidentification. The aim of the present work was to determine the identity of neuron-like cells in immature ovaries of the domestic fowl. Cells immunoreactive to neurofilaments, synaptophysin, and chromogranin-A, with small, dense-core secretory granules, were consistently observed throughout the sub-cortical ovarian medulla and cortical interfollicular stroma. These cells also displayed immunoreactivity for tyrosine, tryptophan and dopamine β-hydroxylases, as well as to aromatic L-DOPA decarboxylase, implying their ability to synthesize both catecholamines and indolamines. Our results support the argument that the ovarian cells previously reported as neuron-like in birds, are neuroendocrine cells.

The effects of cutting gonapophyses were evaluated on the ovarian response two or four days after amputation in imaginai molt decapitated females Blaberus craniifer. Sites binding anti‐egg protein antibodies were detected in the periphery of basal oocytes in 68% operated females. In headless Blaberus craniifer, the onset of vitellogenesis which is triggered by extraphysiological doses of juvenile hormone or indolamines, was induced by this surgical procedure. It is suggested that amputation of gonapophyses affects the delivery of natural messengers inducing vitellogenesis at physiological concentration.

The photoresponses of 116 photoreceptors in the excised perfused pineal body of adult trout were intracellularly recorded. Brief flashes produced slower, but otherwise comparable, responses to retinal receptor cells. The absolute sensitivity, as well as the light-induced membrane conductance changes, were also similar to those of retinal cone cells in the same species. Steady illumination decreased the cell sensitivity to superimposed flashes, in accordance with the Weber-Fechner relation, indicating the presence of light adaptation. This conclusion is supported by the non-exponential nature of the amplitude-intensity relation and by the conspicuous shortening of the time-to-peak with increasing flash intensity. The time-dependent response decay typical of retinal photoreceptors was not found, however. The fact that, during constant illumination, the pineal photoresponses maintain the same amplitude set at the initial peak perhaps represents an original mechanism of light adaptation which allows these cells to maintain their voltage-dependent synthesis and secretion of indolamines as a constant relation with daily illumination.

The pineal gland is known to synthesize numerous indolamines. Since delta-sleep-inducing peptide (DSIP, a tryptophan nonapeptide) is found in the pineal gland, its effect on the secretion of indolamines was investigated. DSIP stimulated melatonin (MEL), 5-methoxytryptophol (5-ML) and serotonin (5-HT) synthesis and release, whereas it did not affect pineal cyclic AMP levels. The stimulatory effect of DSIP on MEL secretion was dose dependent between 5 x 10(-6) and 10(-4) M, whereas the minimal effective concentration of DSIP on 5-ML secretion was higher than 10(-5) M. The effect of DSIP (10(-4) M) was compared to the effect of isoproterenol (ISO, 10(-6) M) on MEL and 5-HT release. ISO stimulated MEL secretion and concomitantly decreased 5-HT release. With regard to kinetic characteristics, the effect of DSIP (10(-4) M) on MEL release was faster and of shorter duration than the effect of ISO (10(-6) M; 2 and 4 h, respectively). At 10(-4) M, DSIP potentiated the ISO-induced increase of MEL secretion. The DSIP-stimulated release of MEL was not significantly altered when the pineal glands were treated with 10(-5) M propranolol (a beta-adrenergic antagonist), 10(-5) M prazosin (an alpha 1-adrenergic antagonist) or 10(-5) M naloxone (an opioidergic antagonist). This study demonstrates that the DSIP-induced secretion of indolamines from rat pineal glands may not be elicited through the well-known noradrenergic or opioid systems.

Bright-light therapy (BLT) is established as the treatment of choice for seasonal affective disorder/winter type (SAD). In the last two decades, the use of BLT has expanded beyond SAD: there is evidence for efficacy in chronic depression, antepartum depression, premenstrual depression, bipolar depression and disturbances of the sleep-wake cycle. Data on the usefulness of BLT in non-seasonal depression are promising; however, further systematic studies are still warranted. In this review, the authors present a comprehensive overview of the literature on BLT in mood disorders. The first part elucidates the neurobiology of circadian and seasonal adaptive mechanisms focusing on the suprachiasmatic nucleus (SCN), the indolamines melatonin and serotonin, and the chronobiology of mood disorders. The SCN is the primary oscillator in humans. Indolamines are known to transduce light signals into cells and organisms since early in evolution, and their role in signalling change of season is still preserved in humans: melatonin is synthesized primarily in the pineal gland and is the central hormone for internal clock circuitries. The melatonin precursor serotonin is known to modulate many behaviours that vary with season. The second part discusses the pathophysiology and clinical specifiers of SAD, which can be seen as a model disorder for chronobiological disturbances and the mechanism of action of BLT. In the third part, the mode of action, application, efficacy, tolerability and safety of BLT in SAD and other mood disorders are explored.

Aromatic L-amino acid decarboxylase (AAAD) is an essential enzyme for the formation of catecholamines, indolamines, and trace amines. Moreover, it is a required enzyme for converting L-DOPA to dopamine when treating patients with Parkinson's disease (PD). There is now substantial evidence that the activity of AAAD in striatum is regulated by activation and induction, and second messengers play a role. Enzyme activity can be modulated by drugs acting on a number of neurotransmitter receptors including dopamine (D1-4), glutamate (NMDA), serotonin (5-HT(1A), 5-HT(2A)) and nicotinic acetylcholine receptors. Generally, antagonists enhance AAAD activity; while, agonists may diminish it. Enhancement of AAAD activity is functional, as the formation of dopamine from exogenous L-DOPA mirrors activity. Following a lesion of nigrostriatal dopaminergic neurons, AAAD in striatum responds more robustly to pharmacological manipulations, and this is true for the decarboxylation of exogenous L-DOPA as well. We review the evidence for parallel modulation of AAAD activity and L-DOPA decarboxylation and propose that this knowledge can be exploited to optimize the formation of dopamine from exogenous L-DOPA. This information can be used as a blue print for the design of novel L-DOPA treatment adjuvants to benefit patients with PD.

The mammalian pineal hormone melatonin (N-acetyl-5-methoxytryptamine), an aminoindole produced by the metabolism of serotonin (5-hydroxytryptamine), has been shown to be a potent scavenger for the highly toxic hydroxyl radical. Three substances that are very important in animal physiology (e.g., in brain metabolism) are noradrenaline, histamine, and serotonin; all three occur in plants. Here we report that serotonin, tryptamine, and melatonin were found in some edible and medicinal plants in Egypt. The results of this screening showed that the pulp of underripe and ripe yellow banana contains 5-hydroxytryptamine at concentrations of 31.4 and 18.5 ng/g, respectively. Corn, rice, barley grains, and ginger showed the highest concentrations of melatonin, at 187.8, 149.8, 87.3, 142.3 ng/100 g, respectively. On the other hand, potato samples were free from all indolamines. Pomegranate and strawberry showed a low level of indolamines (8-12 microg/g serotonin, 4-9 microg/g tryptamine, and 13-29 ng/100 g melatonin).

In this study we investigated the effects of maternal Δ9-tetrahydrocannabinol on the developing serotonergic system. A daily dose of Δ9-tetrahydrocannabinol (5 mg/kg body weight) was administered p.o. to pregnant rats from gestational day 5 to postnatal day 1. Levels of indolamines were measured in four brain areas of the offspring on the day before or after birth. Levels of indolamines depended on the cerebral area, sex and pre- or postnatal age. Maternal exposure to Δ9-tetrahydrocannabinol decreased diencephalic levels of 5-hydroxytryptamine (5-HT), males being more susceptible than females. These perinatal changes could be responsible for the long-term neurophysiological alterations produced by cannabinoids.

Amperometry has been used for real-time electrochemical detection of the quantal release of catecholamines and indolamines from secretory granules in chromaffin and mast cells. Using improved-sensitivity carbon fiber electrodes, we now report the detection of quantal catecholamine release at the surface of somas of neonatal superior cervical ganglion neurons that are studded with axon varicosities containing synaptic vesicles. Local application of a bath solution containing high K+ or black widow spider venom, each of which greatly enhances spontaneous quantal release of transmitter at synapses, evoked barrages of small-amplitude (2-20 pA), short-duration (0.5-2 ms) amperometric quantal "spikes". The median spike charge was calculated as 11.3 fC. This figure corresponds to 3.5 x 10(4) catecholamine molecules per quantum of release, or approximately 1% that evoked by the discharge of the contents of a chromaffin granule.

SummaryEndogenous substances resulting from interactions between alcohol and possibly opioid metabolites and neurotransmitters (dopamine, indolamines) could be mediators of the pathochemical process towards dependence. Beta-carbolines (harman/norharman) are increased in alcoholics and — according to the presented results — in heroin addicts. Psychopathological disorders such as anxiety or depression do not seem to influence the level of beta-carbolines.

Chlordimeform is a relatively new acaricide/insecticide, whose mode of action we have investigated. It appears to interfere with amine-mediated control of nervous and endocrine systems in a variety of ways. Specifically, chlordimeform causes a build-up of the amines 5-hydroxytryptamine and to a lesser extent norepinephrine in the rat brain in vivo, antagonizes the in vivo action of reserpine in the rat (reserpine depletes amine stores in the CNS), inhibits monoamine oxidase from rat liver in vitro, and causes hypotension in rabbits. In the American cockroach it directly stimulates the heart in situ, acts synergistically with tryptamine in vivo, inhibits amine-N-acetyltransferase from cockroach head in vitro, causes accumulation of indolamines in cockroaches in vivo, and blocks the stimulation of adenylate cyclase by octopamine in the cockroach CNS in situ. It also inhibits tryptamine metabolism in whole mites in vitro. Images FIGURE 3. FIGURE 4. A FIGURE 4. B FIGURE 4. C FIGURE 4. D

Dense bodies containing high amounts of chrome were localized in the perikarya of substantia nigra and dorsal raphe neurons following the cytochemical reaction of endogenous dopamine and serotonin (respectively) with glutaraldehyde-dichromate (GDC). Energy dispersive X-ray analysis of these bodies revealed chrome levels two to four times higher than those recorded from the cytoplasmic background. Pretreatment with paraformaldehyde blocked the GDC reaction within the dense bodies in the substantia nigra (chrome levels similar to background), while the chrome levels in the dense bodies of the raphe neurons remained elevated. This demonstrates that pretreatment with paraformaldehyde allows selective localization of central nervous system serotonin stores by the GDC technique.

The present modification of the formaldehyde condensation method for demonstrating catecholamines and indolamines involves generation of the formaldehyde gas at + 80°C followed by reaction at +25 or 0°C. This procedure results in improved sensitivity for demonstrating noradrenaline and dopamine. Because adrenaline and peptides with NH2-terminal tryptophan give no or very weak fluorescence under these reaction conditions the modification also offers possibilities for improved discrimination between primary catecholamines on one hand and adrenaline and tryptophyl peptides on the other. Under the conditions used, the fluorescence yield of 5-hydroxytryptamine did not seem to be improved by variations in the reaction temperature.

The rhythmical activity of the liver fluke, Fasciola hepatica, was stimulated by 5-hydroxytryptamine and by lysergic acid diethylamide at very low concentrations. The effect was peripheral and was not mediated through the central ganglion. Other amines also stimulated rhythmical activity, the most potent being the indolamines. Bromolysergic acid diethylamide, and other analogues such as yohimbine, harmine, and dopamine depressed rhythmical movement and antagonized the stimulant action of 5-hydroxytryptamine and lysergic acid diethylamide. Evidence which suggests the presence of tryptamine receptors in the trematode is discussed.

Adult Syrian hamsters were given a subcutaneous injection of reserpine 3 days before an intraperitoneal injection of 3H-3,4 dihydroxyphenylalanine or 3H-5, hydroxytryptophan and the carotid bodies were subsequently prepared for electron microscopic radioautography. Other Syrian hamsters were given a subcutaneous injection of reserpine and the carotid bodies were subjected to a sensitive cytochemical test for the detection of unsubstituted amines. These studies were made to determine whether the labeled amine precursors were incorporated into the cells and to see whether the parenchymal cells were affected by reserpine treatment. Material from hamsters treated first with reserpine and subsequently injected with 3H-3,4 dihydroxyphenylalanine or 3H-5, hydroxytryptophan exhibited reduced grains of silver over the cells which were associated mainly with the dense cores of the cytoplasmic granules. These studies offer evidence that the granules of the carotid body incorporate catecholamine and indolamine precursors. Material from hamsters incubated for the presence of unsubstituted amines gave a positive reaction (opaque cytoplasmic granules) for catecholamines but not for indolamines. The latter substances may not be present in quantities sufficient to register a positive reaction in the cytochemical test. The opaque granules, indicative of the presence of catecholamines, decreased in density after reserpine treatment. 5 days after one reserpine injection the granules had regained opacity and were comparable to those seen in the control cells.

Considering that glutamatergic axons innervate the C1(Ad) medullary nuclei, which are responsible for the excitation of the peripheral adrenal glands, we decided to investigate catecholamines (noradrenaline, adrenaline and dopamine) plus indolamines (plasma serotonin and platelet serotonin) at the blood level, before and after a small oral dose of amantadine, a selective NMDA antagonist. We found that the drug provoked a selective enhancement of noradrenaline plus a minimization of adrenaline, dopamine, plasma serotonin and platelet serotonin circulating levels. Significant enhancement of diastolic blood pressure plus reduction of systolic blood pressure and heart rate paralleled the circulating parameter changes. The above findings allow us to postulate that the drug was able to enhance the peripheral neural sympathetic activity. Minimization of both adrenal sympathetic and parasympathetic activities was also registered after the amantadine challenge. The above findings supported the postulation that this drug should be a powerful therapeutic tool for treating diseases affected by adrenal sympathetic hyperactivity.

1. Neurons from rat superior cervical ganglia were grown in coculture with pineal cells. Action potentials of neurons in cocultures were 25% longer and were 25% greater in amplitude than those recorded from neurons grown in the presence of ganglionic nonneuronal cells alone. 2. Neurons showed an increase in action potential duration with increasing time in culture. This may have been related to the recovery of nonneuronal cell populations after an initial exposure to the antimitotic agent Ara-C. In cultures not initially exposed to Ara-C, a subsequent exposure after 7 days in culture resulted in a shortening of the action-potential duration. 3. Neuronal cultures were exposed to gel slabs containing the pineal indolamines, serotonin,N-acetylserotonin, and melatonin. Serotonin andN-acetylserotonin showed no effect on the neuronal action potentials at the concentrations tested. 4. Melatonin caused an increase in action-potential duration that was associated not with an increase in action-potential amplitude, but with a decrease in actionpotential rise rates. The effects of long-term exposure in melatonin appeared to be reversible in some cells but not in all. 5. Short-term effects of melatonin were observed in older cultures and in younger cultures after the cells were stimulated repeatedly. Older cultures also had higher levels of spontaneous activity. The dependence of the short-term effects of melatonin on electrical activity may suggest a role for melatonin as a neuromodulator.

Sensory stimuli from the external environment (e.g. visual and olfactory stimuli, stress) or internal stimuli cause brain nerve fibres to release neurotransmitters (catecholamines, indolamines and cholinergic agents). These neurotransmitters regulate the secretion of gonadotrophin-releasing hormone (GnRH) from neurosecretory cells of the hypothalamus (Kamberi, 1975). It would seem that under the proper steroid environment, catecholamines (dopamine, norepinephrine or epinephrine) and the cholinergic agent acetylcholine exert a stimulatory influence, whereas indolamines (serotonin or its metabolic product, melatonin) have an opposite effect. In turn, GnRH reaches the anterior pituitary via the hypophyseal portal system, and, through the mediation of cAMP [though may be not as an obligatory intermediate (Naor et al., 1975)], controls gonadotrophin secretion (Labrie et al., 1974).

The capacity of biogenic amines to form fluorophores in histochemical gas phase reactions has been tested with 20 compounds having a carbonyl group (> C = O) as a common characteristic. Significant visible fluorescence was induced from catecholamines and indolamines with aldehydes, ketones, α-keto acids and carboxylic acids, suggesting that all of these compounds can enter fluorophore-forming cyclization reactions under the histochemical gas phase conditions. The most "reactive" reagents are found among the low molecular aldehydes, and formaldehyde and glyoxylic acid seem to be the most suitable reagents, combining high reactivity with good selectivity. Fluorescence, interesting for the histochemical demonstration of N-acetylated indolamines, was obtained from melatonin and N-acetyl-5-hydroxytryptamine with some acid reagents (glyoxylic acid, formic acid, acetic acid and pyruvic acid). A direct cyclodehydration according to the classical Bischler-Napieralski reaction is the most likely mechanism underlying this fluorophore formation. The usefulness of the various carbonyl reagents for the fluorescence histochemical demonstration of other biologically interesting amines, such as histamine, p-tyramine and octopamine, has been specially investigated.

IT is well known that the neonatal rat brain contains relatively little serotonin1,2 and that the level of this amine increases slowly with age. Karki et al.3 have shown that the enzymes mediating the synthesis and oxidation of serotonin are also low in the immature rat brain, and increase thereafter with growth of the animal. The aforementioned authors suggest that the low levels of indolamines in the rat brain at birth can be attributed to a deficiency of the binding or storage system, and are not a reflexion of the insufficiency of the enzyme systems. Schanberg and Giarman4,5 have shown that endogenous brain serotonin distributes itself between the particulate matter of brain homogenates and the supernatants, and that this relationship is susceptible to alteration by drugs. It was, therefore, of interest to investigate the sub-cellular distribution of serotonin in the developing rat brain and to determine whether it will parallel other maturational changes.

The present paper presents the evaluation of a mixed mode column (reversed phase and cation exchange) performance for the separation of 12 catecholamines, indolamines and their precursors and metabolites. The influence of different parameters, like organic modifier nature and percentage, salts nature and percentage, on the compounds separation was investigated. Good separation of the 12 selected compounds was obtained in the isocratic mode using a mobile phase composed of 90 % methanol and 10% ammonium acetate 20 mM, however the analysis time was excessively long (80 minutes). Thus an elution gradient was optimized and it reduced the analysis time to less than half (35 minutes).