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—We studied the dopamine-, serotonin-, and norepinephrinergic systems in various brain structures of BALB/c male mice on days 15, 42, and 64 of postnatal development (PND) in the model of autism spectrum disorder induced by sodium valproate administration (400 mg/kg, s/c) to pregnant females. It was found that the level of both catechol- and indolamines in the brain structures of control 15-day-old mice is considerably lower than in 64-day-old adult animals. Prenatal administration of sodium valproate (SV) caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of mouse offspring aged 15 days but did not lead to neurochemical changes in other studied brain structures. By PND 42, the general pattern of changes in neurotransmitter concentrations did not differ from the developmental dynamics of neurotransmitter system maturation in the control group. The level of DA kept increasing and by PND 64, did not differ from controls. The parameters of serotonergic system changed similarly, with the peak serotonin concentration by PND 42 and a significant decrease by PND 64, whereas the level of 5-HIAA in the striatum increased gradually with maximum differences observed by PND 64. Thus, the data obtained suggest that administration of SV to pregnant females affects the activity of the dopamine- and serotonergic brain systems in the progeny, inducing its decrease in the striatum by PND 15 followed by recovery to control level by PND 64.

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.

Brain glycogen could be considered as an energy store for neuronal activity, with high relevance in epilepsies. We selected two lines of mice based upon their latency to methionine sulfoximine (MSO) dependent-seizures: MSO-Fast and MSO-Slow, and their neurochemical characterization was attempted in order to look for the mechanisms of epileptogeny. We determined the MSO effect on brain glycogen in the two selected lines and their eight parental strains, and on indolamines and catecholamines. The increase in brain glycogen content induced by MSO is significantly lower in MSO-Fast than in MSO-Slow. At the onset of seizures the degradation of accumulated glycogen was higher in MSO-Slow mice than in MSO-Fast ones. Moreover, a positive correlation was observed between the magnitude of latency toward MSO-induced seizures and brain glycogen content in the eight parental strains used for selection. A striking proportionality between the content of glycogen and 5-hydroxytryptamine (5-HT) was observed in cerebral cortices of both selected lines. However, the cortical 5-HT level is higher in MSO-Fast than in MSO-Slow, and it is significantly decreased at the onset of seizures in both lines. Brain glycogen content is implicated in the developed model of mice with different latency to MSO-dependent seizures: The higher the brain glycogen content, the longer the latency; and 5-HT is involved in the control of latency to seizures-induced by MSO in these two lines. Our model of MSO "sensitive" (MSO-Fast) and "resistant" (MSO-Slow) mice could lead to a better understanding of MSO mechanisms of epileptogenesis, and the relationship between epileptogenic and glycogenic MSO effects.

Hyperglycemia and ketoacidosis are the two most serious factors in acute metabolic complications of both type 1 and type 2 diabetes. Dysfunction of the central nervous system is a well-documented complication of diabetes. We and others have previously reported that acute or chronic diabetes in animal's results in altered brain neurotransmitter levels. In this study, we investigated the effects of acute (7 days) glucose-induced hyperglycemia and sodium acetoacetate (NaAcAc) or ammonium chloride (NH4Cl) induced acidosis on the level of indolamines (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)) as well as PKC-alpha expression/activity in discrete areas of rat brain. Glucose-induced (500 mg/kg, bw) hyperglycemic ( approximately 249 mg%) rats showed significant (p

The purpose of the present study was to evaluate the effect of 4-pregnen-17-hydroxy-3-one (A) and two steroids homologues: 3beta-acetoxy-5,16-pregnadien-20-one (B) and 3beta-acetoxy-16alpha-17alpha-epoxy-4-pregnen-20-one (C). Male Wistar rats were treated with o-cresol combined (A, B or C) steroids. Lipid peroxidation status as result of measurement reactive substances to thiobarbituric acid (TBARS) as well as serotonin (5-HT) and its precursor 5-hydroxytryptophan (5-HTP) were measured. The prostate glands were weighed, the 5alpha-reductase activity was determined. The animals treated with A, B, and C steroids showed a slight increase in both 5alpha-reductase activity and prostate size. 5-HT and 5-HTP levels did not change significantly, and TBARS showed an increase in the group treated with B steroid and a decrease in the A steroid group with significant differences in both groups (p0.05) versus control group. Results suggest that A steroid reduces TBARS in rat brain, perhaps as a result of the interaction between the testosterone unsaturated carbons and OH(-) groups with free radicals.

The serotonin system has been implicated in the modulation of endocrine and behavioral components of reproduction. In this study, we examined endogenous hypothalamic indolamines during sexual differentiation and long-term effects of exogenous steroids during this time. In Experiment 1, Japanese quail were studied during the last half of embryonic development and early post-hatch. Samples were taken at embryonic day 10 (E10), E12, E14, E16, hatch (day 0), and days 3 and 5, post-hatch. Hypothalamic indolamines, including serotonin (5-HT) and its metabolite, 5-hydroxy indole acetic acid (5-HIAA) were measured by HPLC-EC detection. Females had relatively higher hypothalamic 5-HT at E14 than males, with both sexes showing increasing levels thereafter. By day 5, post-hatch, hypothalamic 5-HT content was higher in males than in females. When turnover was estimated by comparing relative concentrations of 5-HT to 5-HIAA, males were significantly higher at E12 and E14 than females. These data suggest that there are stage specific changes in the serotonin system, as well as sexually dimorphic patterns in the ontogeny and activity of this system. In Experiment 2, we investigated the effects of embryonic steroid hormone treatment on the serotonin system and on male sexual behavior. Birds were treated with either estradiol benzoate (EB), testosterone propionate (TP) or sesame oil (vehicle control) at selected embryonic days (E10, E12, E14, E16, 0, D3, and D5). At 4 weeks post-hatch, birds were transferred to short photoperiod (16D:8L) for 3 weeks to prevent photostimulated reproductive development. At 7 weeks of age, males were implanted with a 20 mm silastic capsule filled with testosterone and sexual behavior was tested 1 week later. Brains were collected from both males and females, and preoptic area (POA) indolamines were measured. Steroid treatment at E10 or E12 resulted in the loss of male sexual behavior. Moreover, males treated with EB or TP on E12 also had increased POA 5-HT content as adults, compared to control males. Females treated with EB on either E10 or E 12 also had higher POA 5-HT content than control or TP treated females. These data provide evidence for sexual dimorphism in the hypothalamic 5-HT system at specific stages during embryonic development. Moreover, males were sensitive to exogenous EB and TP on E12, whereas females appeared to be affected by EB only and appeared to be sensitive to steroid effects over a longer period of time in development. Moreover, exogenous steroids at E12 in males also correlated with impaired sexual behavioral. These data suggest that long-term effects of embryonic steroid exposure may be mediated in part through effects on the serotonin neurotransmitter system.

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 secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px), decreased as a result of CP administration, which was restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats; these changes were prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative capacity, however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co-treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function.

Copper toxicity has been implicated in various neurodegenerative disorders such as Wilson's disease and Alzheimer's disease. Free copper in the brain is toxic and leads to neuronal and cellular damage, through free radical generation. Melatonin has been investigated as a possible copper ion chelator. Melatonin could prevent copper-induced neuronal and cellular damage through binding with copper and preventing copper-induced free radical generation. The effect of copper on pineal indolamine synthesis has not been studied extensively. In the present study, copper (2 mg/kg) and melatonin (12 mg/kg) were administered daily to Wistar rats for a 2-week and 6-week period. Pineal organ culture was utilized to monitor pineal indolamine synthesis. The pineals from the 2-week copper/melatonin-treated group showed a statistically significant decrease in 5-methoxytryptophol synthesis (p < 0.01), compared to the pineals from the copper-treated group. Conversly, in the 6-week experiment, 5-methoxytryptophol synthesis was increased in both the copper- and copper/melatonin-treated groups. There was a statistically significant decrease in the N-acetyl serotonin level in the pineals from the 6-week copper-treated animals, as compared to the control- and copper/melatonin-treated group (p < 0.01). These results imply that copper reduces N-acetyltransferase activity, which results in a decrease in N-acetyl serotonin synthesis. Melatonin when coadministered with copper appears to prevent the N-acetyltransferase inhibition by copper. Copper exerts contradictory effects on 5-methoxytryptophol synthesis. Further investigations need to be carried out to examine the effects of copper on the pineal enzymes.

The content of melatonin and its precursors in the pineal gland of healthy rats and rats with hereditary retinal degeneration is studied on days 20 and 40 of postnatal development. The measurements are performed between 02:30 and 03:00, when the content of melatonin is maximal. In December, the content of melatonin and N-acetylserotonin in 20-day-old rats with hereditary retinal degeneration is 1.9- and 3.2-fold higher than in healthy controls. The content of norepinephrine in the pineal gland of these rats is increased 1.8-fold. On postnatal day 40, no differences in the pineal content of indolamines are noted. An increase in the content of melatonin in 20-day-old rats with hereditary retinal degeneration in comparison with healthy controls is also observed in May. A decrease in the maximum nocturnal level of melatonin in May in comparison with December is shown both in rats with hereditary retinal degeneration (by 46%) and healthy controls (by 41%) only on postnatal day 40.

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...

A serotonin N -acetyl transferase (NAT) activity was detected in the brain of Pieris brassicae . The maximal head NAT activity appeared to occur during the wandering-pharate phase. The haemolymph level of serotonin, the selected NAT substrate, presented a maximum on the 3rd day of the 5th instar for both short- and long-photoperiod animals with a longer increase in short-photoperiod animals. The circadian rhythm of head NAT, determined on the same day, appeared bimodal and was affected by pteridines only when they were injected at “specific” times. At the last larval stage, the effect of either serotonin, N -acetylserotonin or melatonin was characterized by inactivity immediately after the injection, leading to death by starvation. In “underchilled” chrysalids, serotonin induced a diapause breakdown while melatonin led to mortality. These data suggest, besides the role of juvenile hormone, ecdysone, and polypeptidic hormones, a role for indolamines during the photoperiodic-dependent development of Pieris .

We studied the effects of four indolamines (melatonin, 5-methoxytryptamine, 5-methoxytryptophol, and 5-methoxytryptophan) on ovarian activity in a tropical rodent, the Indian palm squirrel (Funambulus pennati), during the sexually active phase. Injection of the four 5-methoxyindoles at a dose of 20 μg/0.1 mL per animal every evening for 30 days reduced ovarian mass in both intact and pinealectomized animals. Intact animals treated with 5-methoxyindoles had a lower uterine mass than the intact controls. On the other hand, the uterine mass of pinealectomized animals treated with 5-methoxyindoles did not differ from that of their respective controls. Plasma estradiol levels showed a similar pattern to ovarian masses. We conclude that the effect of 5-methoxyindoles in the female palm squirrel is independent of the pineal gland and that 5-methoxytraptophol and 5-methoxytryptophan are more potent than melatonin.

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.

Migraine is a paroxysmal disorder characterized by recurrent attacks of headache, with or without associated visual and gastrointestinal disturbances. Migraine can be classified in two main groups, common and classic. Theories trying to explain the pathogenesis of a migraine attack may emphasize either the central or peripheral aspects of the disease. The vascular theory may stress the importance of either central or peripheral blood flow or both. Cerebral vasoconstriction in the early phases of the attack is followed by vasodilatation and pain. Biochemical mediators of vascular responses are not exactly known, but platelets and 5-hydroxytryptamine and thromboxane released from them as well as noradrenaline are potent vasoconstrictors, while kinins and prostaglandins can explain the vasodilatory phase of migraine attacks. This review presents evidence for the role of arachidonic acid metabolites, prostaglandins and leukotrienes in migraine. The evidence comes from the measurements of eicosanoids in biological fluids during and after the attack, infusion studies where vasodilatory prostaglandins mimic the migraneous symptoms, and the good effect of non-steroidal anti-inflammatory drugs in the treatment and prophylaxis of migraine attacks. Additional data are based on experimental biochemical studies in which catecholamines and indolamines have been shown to increase the synthesis of vasodilatory prostaglandins. However, the final evidence still awaits its confirmation.

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 study of cerebral ischemia in animals is not easy, because cerebral circulation is not the same as in humans. Indeed, in most animals, there is a collateral circulation between the vertebral and carotid arteries before these arteries enter the brain. On the other hand, in gerbils, unilateral ligation produces ischemia in the ipsilateral forebrain and leads to death in 40–60% of the animals. Because the cerebral ischemia so produced is not effective in all gerbils, it is important to select “sensitive” gerbils by funduscopic examination. Only sensitive gerbils are retained for further experimentation. The nature of the aging process is the subject of some speculation. One hypothesis is referred to as the free radical theory. This theory postulates that free radicals are involved in aging and age-related disorders of the brain. Therefore, we have determined levels of neuromediators involved in cerebral ischemia and memory, including catecholamines (dopamine [DA], dihydroxyphenylacetic acid [DOPAC], hydroxyvanillic acid [HVA]) and indolamines (5-hydroxyindolacetic acid [5HIAA], serotonin [5-HT]), amino acids (aspartate, glutamate and GABA), and free radicals (.OH). We have chosen for study the caudate nucleus, hippocampus, and retina, where changes after ischemia/reperfusion insult are well documented. In gerbil brain, levels of .OH and neurotransmitters are low at birth, reach a plateau, and then decrease with aging. After cerebral ischemia (60 min) induced by left carotid occlusion, the reperfusion (30 min) symptoms are classified using a behavioral score (Stroke Index). Moreover, after ischemia/reperfusion insult (IRI), increases in Stroke Index, .OH, glutamate, aspartate, GABA, monoamines, and indolamines are more pronounced in older gerbils. © 1992 Wiley-Liss, Inc.

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.

As 5 alpha-reductase is involved in the metabolism of indolamines in the Harderian glands of Syrian hamsters, we have compared the effects of androgen deprivation and the administration of the potent 5 alpha-reductase inhibitor N,N-diethyl-4-methoxy-3-oxo-4-aza-5-androstene-17-carboxamida on Harderian porphyrin metabolism. Ten days after castration, porphyrin levels had increased to 40 times the values of intact hamsters. However, the inhibition of 5 alpha-reductase, which resulted in a significant decrease in the weight of accessory sex glands, did not modify porphyrin concentrations within the Harderian glands. It is concluded that, contrary to the situation for indolamine metabolism, testosterone per se is the main androgen involved in the sexual differences observed in Harderian porphyrin metabolism.

1. Apart from octopamine, the same indolamines and catecholamines were detected in the whole nervous system of the cockroach Blaberus craniifer Burm., at the same time. 2. However, levels were found to depend on sex, age, and the anatomic region within the nervous system. 3. Although not established, it is thought that these substances act synchronously from the ganglia. 4. The differences in levels between males and females and between anatomical regions during imaginal life suggest, in this species of cockroach, the physiological importance of the metameric organization in metabolic pathways or functional aspects of biogenic amines.

1. Indolamine levels were determined in the cerebral ganglion, the thoraco-abdominal nerve cord (except the last ganglion), and the 6th abdominal ganglion of females of Blaberus craniifer . 2. Measurements were made at the imaginal molt and on fed and crowded imagos at 10, 20 and 30 post-imaginal days. 3. Indolamines were found in the nervous system of young females, but 5-hydroxytryptophan was only detected in the thoraco-abdominal nerve cord. 4. Amine levels were related to the age of the cockroach, particularly during this period, to post-ecdysi events and ootheca formation.

The effects of different doses of chronically administered carbaryl on rat pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity and pineal and serum melatonin levels during darkness (2300 h and 0100 h) when pineal melatonin synthesis is high were studied. Additionally, pineal levels of 5-hydroxytryptophan (5-HTP), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were estimated. Carbaryl was administered at total doses (over 6 days) of either 50, 125 or 250 mg/kg by gastric gavage. Control rats received vehicle (corn oil) only. During the study, the rats were exposed to light/dark cycles of 14:10 with lights off at 2100 h. Pineal NAT and HIOMT activities and pineal melatonin were increased at 0100 h following carbaryl administration at all three doses. Conversely, serum melatonin was increased at 2300 h after the 250 mg/kg dose of carbaryl while all three doses of the pesticide reduced serum melatonin levels at 0100 h. Pineal 5-HTP, 5-HT and 5-HIAA levels were usually increased at 2300 h but unaffected at 0100 h. The results indicate that carbaryl has significant effects on pineal melatonin synthesis and secretion.

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.

Hyperglycemia and acidosis are the key factors in diabetic complications. It has been shown that acute or chronic diabetes alters serotonin levels in brain. However, the mechanism of hyperglycemia- or acidosis-induced changes in serotonin levels remains poorly understood. Because Ca2+-dependent protein kinases play a major role in the regulation of serotonin synthesis and release, we investigated the effect of diabetes, hyperglycemia, and acidosis on the level of indolamines [5-hydroxytryptamine (5-HT) and/or 5-hydroxyindoleacetic acid (5-HIAA)] and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) enzyme activity or protein expression in different brain regions. Alloxan-induced (45 mg/kg bw) diabetic rats (30 days) showed increased level of 5-HT in striatum (ST; 183%), midbrain (MB; 199%), pons medulla (PM; 151%), cerebellum (CB; 214%), and cerebral cortex (CCX; 162%) compared with control (P < 0.05), and these changes were reversed after insulin administration. Rats treated with glucose (500 mg/kg bw) for 30 days showed a 146%, 183%, 208%, and 177% (P < 0.05) increase in 5-HT levels in ST, PM, CB, and CCX, respectively. 5-HIAA level increased in hippocampus (HC; 172%) and in MB (145%; P < 0.05). In addition, rats treated with sodium acetoacetate (NaAcAc) for 30 days (60 mg/kg bw) showed significant increases (P < 0.05) of 5-HT level in ST (152%) and MB (174%). However, the levels of 5-HIAA increased only in MB (151%, P < 0.05). Rats treated with NH4Cl, which induced acidosis (150 mg/kg bw), showed an increased level of 5-HT only in HC (165%, P < 0.05). The increased activity and protein expression of CaMKII in ST, MB, PM, CB, and CCX under diabetic conditions were correlated with the levels of indolamines changes during diabetic, hyperglycemic, or acidotic conditions. These results suggest that CaMKII may be involved in the regulation of indolamines in diabetic animals. © 2005 Wiley-Liss, Inc.

The purpose of this study was to determine whether the regional brain biogenic amine levels in adult rats were altered by pre- and post-natal exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg per day of 2,4-D from gestation day (GD) 16 to post-partum day (PPD) 23. After weaning, the pups were assigned to one of two subgroups: T1 fed with untreated diet up to post-natal day (PND) 90 and T2 (maintained with 2,4-D diet up to PND 90). In addition, we wanted to know the effect of 2,4-D on lateralization in the monoamine systems of the basal ganglia of these adult rats and whether there was any correlation with the behavioral developmental pattern previously reported by us. In this study the content of noradrenaline (NA) was significantly increased in substantia nigra (SN) while it decreased in cerebellum in male and female rats of T2 group. The decreased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) contents in cerebellum, midbrain, ventral tegmental area (VTA) and prefrontal cortex (PFc) showed an alteration in the mesocorticolimbic system. However, an increase of DA in SN and of DOPAC and HVA in nucleus accumbens (NAc) in both sexes and of DA and DOPAC (only in females) in striatum was detected. The contents of serotonin (5-hydroxytryptamine, 5-HT) were significantly increased in both sexes in PFc, striatum (St), midbrain, SN and cerebellum. Variations of any monoamine levels in NAc and VTA were determined. T1 rats were irreversibly altered: a diminution in DA and/or DOPAC levels in PFc, midbrain, VTA and cerebellum was determined. Indolamines of these rats were increased in both sexes in PFc and St. There was also a large increase in 5-HT levels in midbrain of male rats. Although no changes in the dopaminergic system with respect to their control values in any side of these brain structures were observed, DA and DOPAC levels were found to be decreased in the right side with respect to the left side in striata and accumbens nuclei in T2 female rats supporting the behavioral rotation previously registered by us in these rats. In addition, the increased 5-HT content detected in both the right and left striata observed in this study could be the answer to the behaviors observed and to the early alterations in dopamine in basal ganglia by 2,4-D in neonatal exposed rats, mediated by a serotonergic modulation on the dopaminergic system.

Some catecholamines and indolamines inhibit lipid peroxidation. Recent studies indicate that catecholaminergic inhibition of lipid peroxidation may be receptor mediated in vivo and in cell cultures. Because oxidative stress is one of the hypothesized pathogenic mechanisms for neurodegenerative diseases, including Alzheimer’s disease (AD), we hypothesized that catecholaminergic and indolaminergic inhibition of lipid peroxidation would be altered in AD as compared to age-matched non-AD. To test this hypothesis we studied the effect of a variety of neurotransmitters and their antagonists on ascorbate-stimulated lipid peroxidation in membrane fragment preparations derived from postmortem human brain. In this in vitro system, the inhibition of lipid peroxidation by dopamine and serotonin did not appear to be receptor mediated. Further, our findings indicate that there is no apparent effect of age or AD on the inhibition of lipid peroxidation by catecholaminergic and indolaminergic agents.

Intra-striatal infusion of a high dose (100 microg/3 microl) of methamphetamine produced long-lasting depletions of striatal dopamine and serotonin in both male and female mice. Male mice exhibited a greater depletion of striatal dopamine and serotonin than female mice. A similar trend of sexual differences was observed when 4 cumulative doses of methamphetamine were administered systemically. Thus, the sexual differences in methamphetamine-induced neurotoxicity in the striatum are probably not due to their differences in peripheral metabolism of methamphetamine. Moreover, ovariectomized (OVX) mice supplemented with 3 daily doses of estradiol benzoate (EB) at high or physiological levels, 3 daily doses of progesterone (P), and 2 doses of EB followed by 1 dose of P all demonstrated higher striatal dopamine levels following methamphetamine treatment as compared to vehicle-supplemented controls. The OVX mice pretreated with 3 daily doses of P exhibited the highest striatal serotonin levels after methamphetamine administration of all groups. In conclusion, sexual differences observed in methamphetamine-induced striatal neurotoxicity may be modulated by ovarian hormones.

To determine whether sustained hypoxia alters daily rhythms in brain and pituitary neurotransmitters, the daily variations in vasoactive intestinal peptide-like immunoreactivity (VIP-LI), neuropeptide Y-like immunoreactivity (NPY-LI), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) content were determined in discrete brain regions, pineal gland and anterior pituitary of hypoxic (10% O2; 14 days) and normoxic rats. Hypoxia suppressed daily variations in VIP-LI in the suprachiasmatic nuclei (SCN) and the anterior pituitary, enhanced the daily rhythmicity in serotonergic elements of the caudal part of the dorsomedial medulla oblongata (DMMc), and even induced daily variations in NPY-LI in the DMMc as well as in the ventrolateral medulla oblongata. In addition, punctual alterations in the rhythmicity of 5-HT and 5-HIAA in the pineal gland and of plasma corticosterone were observed in hypoxic rats. Thus results of this study indicate that a permanent nonphotic stimulus, such as sustained hypoxia, may affect the functioning of the internal clock located in the SCN and may alter the daily rhythmicity in neurotransmitter content of some brain nuclei and the pituitary gland.

Tetrahydrobiopterin (BI-L) is the cofactor for the pteridine-de~ndent monoxygenases (phenylalanine tyrosine and tryptophan hydroxylases) (Kaufmann and Fisher 1974), which play important roles in the biosynthesis of biogenic amines such as catecholamines and indolamines. The biosynthesis of these biogenic amines is regulated by the hydroxylat~on reaction of amino acids such as tyrosine and tryptophan (Nagatsu et al. 1964; Lovenberg et al. 1967), and this hydroxylation reaction is regulated by the concentration of BH4 (Kettler et ~J. !974). These biogenic amines, especially noradrenaliE.e and serotonin, have been thought to be related to affective disorders (Van Praag 1982). Therefore, the relationship between BH4 and depression has been of particular interest, and some controversial results about this relationship have been reported: lowering of the BI-L~ synthesi,~ in the postmortem brains of patients with depression (Blair et al. 1984); no difference between the CSF biopterin levels in patients with depression and in normal controls (Kellner et al. 1980; Levine and Lovenberg 1984); an in

Long-term hypoxia induces changes in neuropeptide-Y-like immunoreactivity (NPY-LI) and/or in the content of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) at the central level. To determine whether these alterations depend on the integrity of carotid body (CB) chemoreceptors, intact rats or those whose carotid sinus nerve was transected (CSNT) were exposed to hypoxia (10% O2) or to normoxia for 14 days. Thereafter, NPY-LI, 5-HT and 5-HIAA levels in discrete brain regions were determined. The increase in NPY-LI in the ventrolateral medulla oblongata (VLM) of intact hypoxic rats was mostly abolished after CSNT and therefore is mainly mediated by CB chemoreceptors. In contrast, other hypoxia-induced changes were similar or even enhanced in CSNT as compared to intact rats and therefore do not depend on the integrity of CB chemoreceptors. This was the case for the increase of NPY-LI in the striatum and the caudal dorsomedian medulla oblongata (DMM), as well as for all the changes in 5-HT and 5-HIAA in the DMM, the VLM, the raphe nuclei, the striatum and the frontal cortex. We propose that long-term hypoxia alters brain NPY-LI and indolamine content through the stimulation of CB chemoreceptors or ancillary chemoreceptors, as well as through local biochemical or morphological mechanisms.

Melatonin is an antioxidant. Since other antioxidants inhibit the production of tumor necrosis factor (TNF) induced by lipopolysaccharide, we investigated its effect on TNF production in vivo and in vitro and on lethality associated with endotoxic shock. Administration of melatonin to mice (5 mg/kg, s.c., 30 min before or simultaneously with lipopolysaccharide) inhibited serum TNF levels by 50-80% and improved survival of mice treated with a lethal dose of lipopolysaccharide. By studying other, structurally related, indolamines (N-acetyl-5-hydroxytryptamine, 5-methoxytryptamine and 5-hydroxytryptamine) we found a good correlation between antioxidant activity (for which the 5-methoxy group is essential) and the inhibition of TNF production in vivo and in vitro in mononuclear cells. Melatonin did not increase serum corticosterone and did not modify the elevation of serum corticosterone levels by lipopolysaccharide or by interleukin-1. Furthermore, it exerted its inhibitory effect in adrenalectomized or hypophysectomized mice also, indicating that its effect is independent of the hypothalamus-pituitary-adrenal axis.

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.

The administration of purified cytokines to animals has been shown to cause a number of effects on the brain, including neuroendocrine effects, behavioral effects and alterations of brain biogenic amines. The best-documented effects are the activation by interleukin-1 (IL-1) of the hypothalamo-pituitary-adrenocortical (HPA) axis, and cerebral norepinephrine and indolamine metabolism. IL-6 and TNF alpha may also activate the HPA axis, and IL-6 activates cerebral indolamines. There are a few reports of other responses, but for proper evaluation it is important that studies be conducted using purified homologous cytokines, free of endotoxin contamination. The effects of the cytokines on the brain are believed to be a major mechanism by which infections and immune challenges signal the brain and activate endocrine and behavioral responses. The noradrenergic responses to IL-1 may be related to HPA activation, but the significance of the indolaminergic responses is unknown.

Parathion, an organophosphorous insecticide, was previously shown to enhance the nighttime rise in pineal N-acetyltransferase (NAT) activity and serum melatonin levels. The purpose of the present study was to test whether parathion acts on the pineal gland by means of a beta-adrenergic receptor mechanism. Whereas parathion (total dose 6.5 mg/kg body wt over 6 days) by itself significantly augmented nocturnal pineal NAT activity and serum melatonin levels in otherwise untreated rats, the insecticide was ineffective in reference to this enzyme when it was given in conjunction with the beta-adrenergic receptor antagonist propranolol (20 mg/kg body wt, 1 h before lights off). The augmentation of NAT activity by parathion also caused significant reductions in pineal serotonin (5-HT); again, this response was blocked by propranolol treatment. Neither pineal hydroxyindole-O-methyltransferase (HIOMT) activity nor pineal levels of 5-hydroxytryptophan or hydroxyindole acetic acid (5-HIAA) were significantly changed as a result of either parathion or propranolol treatment. The results are consistent with the idea that parathion influences pineal 5-HT metabolism either at the level of the beta-adrenergic receptor or via the sympathetic innervation to the pineal gland.

In vivo microdialysis was used to measure changes in extracellular concentrations of catecholamines and indolamines in freely moving rats in response to administration of endotoxin (lipopolysaccharide, LPS). Dialysis probes were placed stereotaxically in either the medial hypothalamus or the medial prefrontal cortex. We used a repeated-measures design in which each rat received LPS or saline, and each subject was retested with the other treatment one week later. With the dialysis probes in the medial hypothalamus, intraperitoneal (ip) administration of LPS (5 micrograms) increased dialysate concentrations of norepinephrine (NE, 187%), dopamine (DA, 119%), and all their measured catabolites, except normetanephrine. Dialysate concentrations of NE and DA were elevated significantly in the fourth or fifth (20 min) collection period with a peak response at around 2 hr. They returned to baseline by about 4 hr. When the dialysis probes were placed in the medial prefrontal cortex, the same dose of LPS also elevated dialysate concentrations of NE and DA, but the increases were much smaller (ca. 20%). However, a dose of 100 micrograms LPS increased dialysate concentrations of NE and DA from the medial prefrontal cortex to an extent comparable to that of the 5 micrograms dose in the hypothalamus, and the response was more prolonged. Dialysate concentrations of serotonin could not be measured reliably, but those of its catabolite, 5-hydroxyindoleacetic acid (5-HIAA), were also elevated in both regions. The peak of 5-HIAA occurred at around 4 hr. Pretreatment of the rats with indomethacin (10 mg/kg ip) completely prevented the changes due to 100 micrograms LPS in the medial prefrontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Aromatic L-amino acid decarboxylase (AADC) is involved in the biosynthesis of catecholamines and indolamines. AADC is present in the nervous system, in the chromaffin cells, and in non-neuronal tissues. We tested the capacity of a new polyclonal antibody, obtained by immunization of rabbits with a recombinant protein β-galactosidase-AADC, to detect monoaminergic neurons in the brainstem as well as monoaminergic paraneurons in the adrenal medulla from goldfish, frog, skink, quail, and mouse. In the adrenal gland we found an immunoreactivity that was consistent with the distributions of the chromaffin cells previously reported. In the brainstem, groups of immunoreactive neurons and several labelled fibers were observed in the five species studied. The raphe region showed cell bodies and processes similar to those previously identified as monoaminergic by other authors. In addition, in medulla oblongata and isthmic tegmentum we found, in goldfish, skink, and quail, neuronal groups similar to mammalian D groups which contain AADC but are devoided of serotonin and catecholamines.

Publisher Summary The chapter describes the experiments of intracellular recording from pineal photoreceptors of the trout. The hyperpolarizing nature of their photoresponses, similar to retinal photoreceptors, are confirmed and presents evidence that they are the result of a membrane conductance decrease, as reported in preliminary form. In addition, 3 isobutyl-1-methylxantine (IBMX), a potent phosphodiesterase inhibitor alters the photo responses in accordance with the effects observed in the amphibian retina. A significant difference between the two photoreceptor types with regard to their light adaptation properties was found. Thus, pineal photoreceptors produce constant amplitude responses to prolonged illumination, without showing the characteristic, time-dependent membrane potential changes measured in retinal receptor cells under similar circumstances. These results are discussed in relation to the pineal photoreceptor role in the synthesis and secretion of indolamines.

Monoamine oxidase (MAO) is a mitochondrial enzyme responsible for the oxidative deamination of catecholamines and indolamines (Alexopoulos et al 1984). Plate!ets contain only MAO-B, whereas human brain contains both MAO-A and MAO-B (Po~,rier et al 1987). The kinetics of platelet MAO-B are believed to be similar to central turnover of monoamines (Georgotas et al 1986), but Young and colleagues (1986) found no connection between platelet and brain MAO-B. Nevertheless, this controversial area has been implicated in attempts to identify a biological marker tbr the evaluation of the size or capacity of the central serotonin system (Hailman et al 1990). In this study we examined platetet MAO-B activity as a biological marker tbr depressive and anxiety disorders, giving par.icular attention to its relation to age of onset.

1. Indolamines were assayed by HPLC-ECD in nervous tissue of fed and crowded young males Blaberus craniifer Burm. 2. In males, as in females housed in the same conditions, levels are depending on both age and region (= ganglia) of the central nervous system. 3. Registered sex differences are discussed in terms of anatomical, physiological and behavioral sexual dimorphism.

1. The effects of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and N -acetyl-5-hydroxytryptamine on oocytes of Blaberus craniifer , in which vitellogenesis was prevented by imaginal molt decapitation, were investigated. 2. Sites binding anti-egg-protein antibodies were detected in the periphery of basal oocytes of treated females, with individual variability. 3. In this ovoviviparous cockroach, the onset of vitellogenesis may thus not be triggered solely by juvenile hormone, and indolamines may play a role in the uptake of haemolymphatic proteins by oocytes.

The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious, changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin, 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.

Temporal changes in monoaminergic activity in the locus coeruleus (LC) in response to hemorrhage of 10 or 20% of blood volume were assessed using normal pulse voltammetry in alpha-chloralose-urethan-anesthetized cats. Oxidation current was measured with a carbon microelectrode, and changes at 230 and 450 mV were used as estimates of catecholaminergic and indolaminergic activity, respectively. Plasma adrenocorticotropin (ACTH) was measured by radioimmunoassay. Hemorrhage of 20% blood volume caused a transient increase in the catecholaminergic activity in a compact area in the ventral LC (vLC) that preceded increases in the plasma ACTH. The increase in oxidation current at 450 mV was similar to that at 230 mV, suggesting no significant contribution from indolamines. Dorsal rostral pontine sites outside this area exhibited either sustained decreases in oxidation current or no change in response to hemorrhage. The proportion of sites that exhibited transient increases in oxidation current in the vLC after the 10% blood loss was less than that after the 20% blood loss, suggesting that this response was dependent on the magnitude of hemorrhage. Since the LC was implicated previously in the control of ACTH release, we suggest that hemodynamic signals traversing the LC activate catecholaminergic mechanisms that, in turn, participate in the regulation of ACTH release after hemorrhage.

Kynuramines occur endogenously in brain and peripheral tissues as metabolites of indoleamino acids and indolamines but little is known regarding their possible physiological and/or pharmacological activity. The present study has investigated the effects of kynuramine and 5-hydroxykynuramine on the cardiovascular system of pithed rats and attempted to correlate effects seen on adrenergic and serotonergic receptors with ligand binding experiments done in vitro using rat brain membranes. Kynuramine was found to release cardiac catecholamines and to act as a weak partial agonist on vascular alpha-adrenoceptors. Hydroxylation in the 5-position (5-hydroxykynuramine) did not alter cardiac potency but increased pressor activity 100-fold. Vasopressor responses to 5-hydroxykynuramine were mediated via a dual agonistic action on both postsynaptic alpha 2-adrenoceptors and vascular serotonin2 receptors. These findings were supported by ligand binding studies, in which both kynuramine and 5-hydroxykynuramine showed affinity for cortical [3H]spiroperidol and [3H]clonidine binding sites. Overall, the results show that kynuramines can exert peripheral (and possibly central) actions which may prove to be of physiological and/or pharmacological significance.

The effect of indolamine derivatives on beta-endorphin (beta-end) release has been studied in vitro using rat anterior pituitary cells. Incubation of primary cultures for 2 h with 100 nmol/l of melatonin, serotonin or 5-methoxytryptamine significantly increased the beta-end release in response to 20 nmol/l of ovine corticotropin-releasing factor (oCRF). Incubation of the cultures with 100 nmol/l of L-tryptophan, 5-hydroxy-L-tryptophan, 5-hydroxytryptophol or 5-methoxytryptophol had no effect on basal or CRF-induced beta-end release. The effect of serotonin and melatonin was further tested in a superfusion system of dispersed rat anterior pituitary cells. Superfusion with oCRF (200 nmol/l) for 4 min elicited an immediate rapid increase in beta-end release which lasted 30-40 min. Simultaneous superfusion with melatonin (1 mumol/l) or serotonin (1 mumol/l) significantly increased the effect of oCRF pulses on beta-end release. We conclude that melatonin and serotonin are able to act directly on anterior pituitary cells to potentiate the effect of oCRF on beta-end release.

Low MAO activity has been reported in a number of studies to be lower in patients with chronic schizophrenia (see recent review by WYATT and MURPHY,~ cotwins of schizophrenic@ as well as in patients with bipolar (manic depressive) disorders3 .Since MAO is an important enzyme in the degradation of both catecholamines and indolamines, low MAO in schizophrenics would be consistent with two of the leading conceptualizations of biochemical abnormalities in the major psychoses-the transmethylation and dopamine hypotheses. Further, platelet MAO activity is under genetic control as shown by studies of twins.4,5

The hypothalamus exerts an inhibitory influence on prolactin release from the anterior pituitary. Whether or not peptide hypothalamic prolactin-regulating factors, analogous to those for other pituitary hormones, exist, remains to be confirmed. There is evidence that catecholamines and indolamines directly or indirectly affect prolactin release, This concept may explain the pathogenesis of galactorrhœa-amenorrhœa and other endocrine diseases produced by hypothalamic-pituitary disorders.