UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tandospirone citrate (tandospirone) is an anti-anxiety drug that acts by combining with serotonin receptor (5-hydroxytryptamine-1 A [5-HT1A]). Recently, there have been a few reports of its potential role in the treatment of cerebellar ataxia. We report the first case of a patient with Machado-Joseph disease in which we successfully treated cerebellar ataxia. In addition, his leg pain, insomnia, anorexia, and depression, which are thought to be related to 5-HT1A receptors, were also remarkably alleviated by treatment with tandospirone.
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PMID:Beneficial effects of tandospirone on ataxia of a patient with Machado-Joseph disease. 1195 22

A quantitative analysis of two rat syndromes of myoclonus are presented, modeling myoclonic epilepsy and postanoxic myoclonus. Like the human conditions, both of the models benefit therapeutically from drugs that act on the serotonin system. The rat model of myoclonic epilepsy is associated with a profound loss of serotonin throughout the brain (except in the striatum) and is generated by an oscillator that is synchronized around the midline. The rat model of posthypoxic myoclonus does not demonstrate a significant reduction in serotonin in any location of its brain and is generated by a non-oscillating circuit in the medulla. Although some forms of myoclonic epilepsy may benefit from serotonin drugs because they are caused by a decrease in brain serotonin, our data indicate that posthypoxic myoclonus is not caused by a decrease in the serotonergic innervation of any region of the brain. That the raphe nuclei do not degenerate after global brain ischemia was noted by C. David Marsden in a discussion of the histologic findings of three of his human cases of posthypoxic myoclonus (page 117 of reference 10) and led him to question the hypothesis that posthypoxic myoclonus was due to a loss of serotonin neurons. Our data confirm his observation in the rat, but also indicate that density of serotonin fibers and terminals throughout the brain is not reduced by the brain ischemia that produces posthypoxic myoclonus. It remains to be determined whether the physiologic responsiveness of serotonin neurons is altered by global brain ischemia and whether changes in serotonin release or serotonin receptor properties are associated with posthypoxic myoclonus. The stability of the serotonin system in posthypoxic myoclonic rats is remarkable when one considers the wide range of disorders that is produced by the prolonged brain ischemia. The inability of the most severely posthypoxic myoclonic rats to perform 7-Hz tongue protrusions indicates substantial physiologic disruption of brainstem motor function. Moreover, the posthypoxic myoclonic rat suffers from ataxia, seizures, retrograde amnesia, and impaired ability to learn. The wide spectrum of these deficits is sharply constrasted by its apparently intact serotonin system. We have identified the inferior olive as a locus that may generate the rhythmic components of tremor and myoclonus in syndromes that are truly associated with a dramatic loss of brainstem serotonin. Serotonin acts within the inferior olive to constrain its rhythmic firing. Without intraolivary serotonin, olivary neurons are predisposed to oscillate continuously, providing a substrate upon which sustained rhythmic spiking may be superimposed. It is clear that such unconstrained rhythmicity produces synchronized whole-body tremor at 10 Hz (33, 41-43). The effects of serotonin to suppress olivocerebellar rhythmicity are mediated by postsynaptic 5-HT2 receptors that reduce the magnitude of the low-threshold calcium conductance, IT. It is notable that dysregulation of this conductance has been associated with hyper-rhythmic states in the thalamus underlying cognitive disorders ranging from depression to tinnitus (49), indicating a common mechanism underlying a variety of neurologic conditions. The identification of a specific brainstem locus (inferior olive), serotonin receptor 5-HT2, and ionic current IT involved in a form of rhythmic myoclonus may provide multiple clues toward which future pharmacotherapies can be directed.
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PMID:The serotonin hypothesis of myoclonus from the perspective of neuronal rhythmicity. 1196 57

A growing body of evidence demonstrates the efficacy of Garcinia cambogia-derived natural (-)-hydroxycitric acid (HCA) in weight management by curbing appetite and inhibiting body fat biosynthesis. However, the exact mechanism of action of this novel phytopharmaceutical has yet to be fully understood. In a previous study, we showed that in the rat brain cortex a novel HCA extract (HCA-SX, Super CitriMax) increases the release/availability of radiolabeled 5-hydroxytryptamine or serotonin ([3H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior and appetite control. The aim of the present study was 2-fold: (a) to determine the effect of HCA-SX on 5-HT uptake in rat brain cortex in vitro; and (b) to evaluate the safety of HCA-SX in vivo. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min and transferred to buffer solutions containing [3H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA-SX (10 microM - 1 mM) and the serotonin receptor reuptake inhibitors (SRRI) fluoxetine (100 microM) plus clomipramine (10 microM). Uptake of [3H]-5-HT was expressed as d.p.m./mg wet weight. A time-dependent uptake of [3H]-5-HT occurred in cortical slices reaching a maximum at 60 min. HCA-SX, and fluoxetine plus clomipramine inhibited the time-dependent uptake of [3H]-5-HT. At 90 min, HCA-SX (300 microM) caused a 20% decrease, whereas fluoxetine plus clomipramine inhibited [3H]-5-HT uptake by 30%. In safety studies, acute oral toxicity, acute dermal toxicity, primary dermal irritation and primary eye irritation, were conducted in animals using various doses of HCA-SX. Results indicate that the LD50 of HCA-SX is greater than 5,000 mg/kg when administered once orally via gastric intubation to fasted male and female Albino rats. No gross toxicological findings were observed under the experimental conditions. Taken together, these in vivo toxicological studies demonstrate that HCA-SX is a safe, natural supplement under the conditions it was tested. Furthermore, HCA-SX can inhibit [3H]-5-HT uptake (and also increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of SRRIs, and thus may prove beneficial in controlling appetite, as well as treatment of depression, insomnia, migraine headaches and other serotonin-deficient conditions.
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PMID:Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). 1234 13

Ziprasidone is a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The initial evidence suggests an effective dosage range of 80-160 mg/day. Clinical trials suggest that the drug is an effective antipsychotic in schizophrenia and schizo-affective disorder with a beneficial effect on negative symptoms and symptoms of depression. The main adverse effects appear to be somnolence (14%) and nausea (10%). Ziprasidone has relatively fewer side effects and yet has at least equivalent efficacy for florid 'positive' symptoms compared to conventional anti psychotics. The additional serotonergic actions deliver further efficacy against 'negative' and affective symptoms of schizophrenia. Reduced effects on cognitive abilities compared to conventional anti psychotics make Ziprasidone more attractive.
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PMID:Brief report on Ziprasidone. 1239 87

Serotonin (5-hydroxytryptamine, 5-HT) mediates a wide variety of physiological functions by activating multiple receptors, and abnormalities of these receptor systems has been implicated in many psychiatric disorders including anxiety, depression, psychosis, migraine, disorders of sexual functioning, sleep, cognition, and feeding. Many of the currently used treatments for these disorders act by affecting the serotonergic system. Observation of serotonin receptor alterations, before and following effective treatments, may yield important insights into the aetiology of these psychiatric disorders and may ultimately lead to more selective and effective therapies. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:A review of the role of serotonin receptors in psychiatric disorders. 1240 2

Since its discovery 50 years ago, the role of the indoleamine 5-HT (5-hydroxytryptamine; serotonin) in the pathogenesis of depression and in the mechanism of action of antidepressant drugs has been the subject of considerable research. Advances in molecular biology and radioligand techniques have led to the functional characterisation of at least 14 serotonin receptor subtypes. This classification has led to the development of selective compounds that have aided in the efforts of dissecting the complex role of 5-HT in depression and in mediating the antidepressant response. This review focuses largely on novel strategies of targeting specific 5-HT receptors subtypes, especially the presynaptic 5-HT(1A) and 5-HT(1B/1D) receptors. These subtypes are of primary importance in that they control the firing of the 5-HT neuron and the release of 5-HT. In addition, a number of postsynaptic 5-HT receptors have been shown to be dysfunctional in depression and are also potential targets for a number of antidepressants. We conclude that selective targeting of 5-HT receptors may lead to a faster acting and more efficient antidepressant response. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response. 1240 40

The 5-HT(1A) receptor is a well-characterized serotonin receptor playing a role in many central nervous functions and known to be involved in depression and other mental disorders. In situ hybridization, immunocytochemical, and binding studies have shown that the 5-HT(1A) receptor is widely distributed in the rat brain, with a particularly high density in the limbic system. The receptor's localization in the different neuronal subtypes, which may be of importance for understanding its role in neuronal circuitries, is, however, unknown. In this study we show by immunocytochemical double-labeling techniques, that the 5-HT(1A) receptor is present on both pyramidal and principal cells, and calbindin- and parvalbumin-containing neurons, which generally define two different subtypes of interneurons. Moreover, semiquantitative analysis showed that the receptor's distribution in the different neuronal types varies between brain areas. In cortex, hippocampus, hypothalamus, and amygdala the receptor was located on both principal cells and calbindin- and parvalbumin-containing neurons. In septum and thalamus, the receptor was mostly present on calbindin- and parvalbumin-containing cells. Especially in the medial septum and thalamic reticular nucleus, the receptor highly colocalized with parvalbumin-positive neurons. These results suggest a diverse function of the 5-HT(1A) receptor in modulating neuronal circuitry in different brain areas, that may depend on the type of neuron the receptor is predominantly located on.
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PMID:The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain. 1248 Jan 58

Definitive conclusions on the role of serotonin receptors and transporter in suicide and depression have been elusive in studies of postmortem brain tissue. A number of methodological differences in these studies have made it difficult to reach a consensus, but crucial issues are being identified and incorporated into newer studies. This review will follow the evolution of serotonin receptor and transporter studies in postmortem tissues that initially focused on suicide and gradually incorporated depressive disorders as psychiatric assessments were increasingly performed. Studies in postmortem tissues on the serotonin-1A and serotonin-2A receptors and the serotonin transporter will be reviewed and compared with imaging studies of the same sites in depressed subjects. Critical issues to control in future studies of serotonin receptors in postmortem tissues include variables such as the cause of death (i.e. suicide), the specific psychiatric diagnoses of the subjects, whether the disorder was in remission at the time of death, long-term medication histories, psychoactive substance use disorders, the smoking history, the hemisphere from which tissues were dissected, and the specific cytoarchitectonic region to be evaluated. Carefully controlled studies in postmortem tissues will ensure a greater likelihood of reaching a consensus on the involvement of monoamine measures in the etiology of depression.
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PMID:Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. 1284 29

All respiratory long-term facilitation (LTF) is induced by inspiratory-excitatory stimulation, suggesting that LTF needs inspiratory augmentation and is the result of a Hebbian mechanism (coincident pre- and post-synaptic activity strengthens synapses). The present study examined the long-term effects of episodic inspiratory-inhibitory vagus nerve stimulation (VNS) on phrenic nerve activity. We hypothesized that episodic VNS would induce phrenic long-term depression. The results are compared with those obtained following serotonin receptor antagonism or episodic carotid sinus nerve stimulation (CSNS). Integrated phrenic neurograms were measured before, during and after three episodes of 5 min VNS (50 Hz, 0.1 ms), each separated by a 5 min interval, at a low (approximately 50 microA), medium (approximately 200 microA) or high (approximately 500 microA) stimulus intensity in anaesthetized, vagotomized, neuromuscularly blocked and artificially ventilated rats. Medium- and high-intensity VNS eliminated rhythmic phrenic activity during VNS, while low-intensity VNS only reduced phrenic burst frequency. At 60 min post-VNS, phrenic amplitude was higher than baseline (35 +/- 5% above baseline, mean +/- S.E.M., P < 0.05) in the high-intensity group but not in the low- (-4 +/- 4%) or medium-intensity groups (-10 +/- 15%), or in the high-intensity with methysergide group (4 mg kg(-1), i.p.) (-11 +/- 5%). These data, which are inconsistent with our hypothesis, indicate that phrenic-inhibitory VNS induces a serotonin-dependent phrenic LTF similar to that induced by phrenic-excitatory CSNS (33 +/- 7%) and may require activation of high-threshold afferent fibres. These data also suggest that the synapses on phrenic motoneurons do not use the Hebbian mechanism in this LTF, as these motoneurons were suppressed during VNS.
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PMID:Episodic phrenic-inhibitory vagus nerve stimulation paradoxically induces phrenic long-term facilitation in rats. 1287 10

Neuromodulation is often thought to have a static, gain-setting function in neural circuits. Here we report a counter example: the neuromodulatory effect of a serotonergic neuron is dependent on the interval between its spikes and those of the neuron being modulated. The serotonergic dorsal swim interneurons (DSIs) are members of the escape swim central pattern generator (CPG) in the mollusk Tritonia diomedea. DSI spike trains heterosynaptically enhanced synaptic potentials evoked by another CPG neuron, ventral swim interneuron B (VSI-B), when VSI-B action potentials occurred within 10 sec of a DSI spike train; however, if VSI-B was stimulated 20-120 sec after DSI, then the amplitude of VSI-B synaptic potentials decreased. Consistent with this, VSI-B-evoked synaptic currents exhibited a temporally biphasic and bidirectional change in amplitude after DSI stimulation. Both the DSI-evoked enhancement and decrement were occluded by serotonin and blocked by the serotonin receptor antagonist methysergide, suggesting that both phases are mediated by serotonin. In most preparations, however, bath-applied serotonin caused only a sustained enhancement of VSI-B synaptic strength. The heterosynaptic modulation interacted with short-term homosynaptic plasticity: DSI-evoked depression was offset by VSI-B homosynaptic facilitation. This caused a complicated temporal pattern of neuromodulation when DSI and VSI-B were stimulated to fire in alternating bursts to mimic the natural motor pattern: DSI strongly enhanced summated VSI-B synaptic potentials and suppressed single synaptic potentials after the cessation of the artificial motor pattern. Thus, spike timing-dependent serotonergic neuromodulatory actions can impart temporal information that may be relevant to the operation of the CPG.
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PMID:Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit. 1464 66

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