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

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.
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PMID:Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates. 778 83

Serotonin (5-hydroxytryptamine; 5-HT) has been implicated in a large number of psychophysiologic processes including the regulation of sleep, appetite, mood, aggression, perception, memory, and anxiety. To mediate this large array of physiologic processes, at least 14 separate 5-HT receptors have evolved, which are divided into seven main families. Not surprisingly, alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including anxiety, depression, eating disorders, schizophrenia, personality disorders, and many drug-induced psychotic states. Additionally, a number of effective psychopharmacologic agents for diseases as diverse as schizophrenia and anxiety have been developed which either specifically alter brain levels of serotonin or bind to 5-HT receptor subtypes. This review article summarizes recent advances in the burgeoning field of serotonin receptor pharmacology and integrates this information into a coherent perspective on the importance of serotonergic agents for clinical psychiatry.
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PMID:Multiple serotonin receptors: clinical and experimental aspects. 780 91

The participation of serotonin (5-HT) in the regulation of diverse biological and psychological functions makes it possible for medications acting on 5-HT subsystems to play a role in the treatment of a growing number of psychiatric and medical disorders. The actions of new medications on the 5-HT reuptake mechanism are complemented by actions on the 5-HT receptors and on other neurotransmitter systems that may be effective in complex and treatment-resistant syndromes. New drugs acting on one or more of the seven major 5-HT receptor classes that have been identified thus far appear to be promising for the treatment of specific subtypes of psychiatric syndromes, from depression to anxiety to schizophrenia. A given serotonergic medication may be useful for more than one disorder because it acts on specific dimensions of psychobiological malfunction that characterize more than one disorder, dimensions that are mediated by more than one receptor.
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PMID:Serotonergic mechanisms and current and future psychiatric practice. 784 6

The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists. The results, together with our previous findings, indicate an apparent rank order of potency: 5-carboxamidotryptamine (5-CT) > sumatriptan > methysergide > 5-HT >> 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) > 5-methoxytryptamine (5-MeOT) = 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) > alpha-methyl-5-hydroxytryptamine (alpha-Me 5-HT) >> (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The equipotent molar ratios were 5-CT 0.12, sumatriptan 0.4, methysergide 0.72, 5-HT 1.0, 8-OH-DPAT 13.3, 5-MeOT 26.7, TFMPP 31, alpha-Me 5-HT 402 and DOI > 3333. Time for peak depression from start of agonist application was 3-4 min for 5-HT, 5 min for sumatriptan and 5-MeOT, 5-7 min for alpha-Me 5-HT and 12 min for 8-OH-DPAT. The half-time for recovery from peak depression was 1.5 +/- 0.3 min for 5-HT, 2.8 +/- 0.3 min for 5-MeOT, 5.3 +/- 1.5 min for sumatriptan, 13 +/- 2.9 min for 8-OH-DPAT and > 30 min for alpha-Me 5-HT. 8-OH-DPAT induced depression of the reflex (IC50 0.85, 0.7-1.0 microM, geometric mean and 95% confidence limits) was blocked by spiperone (1 microM, apparent pA2 6.3) suggesting mediation via 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A novel 5-HT receptor or a combination of 5-HT receptor subtypes may mediate depression of a spinal monosynaptic reflex in vitro. 796 10

Numerous observations support the notion that serotonin (5-hydroxytryptamine; 5-HT) and its multiple receptor subtypes are linked not only to the biological basis of depression, but also to the mechanism of action of antidepressant drugs. A general hypothesis of 5-HT receptor dysregulation in depression suggests that 5-HT1A receptors may be down-regulated, whereas 5-HT2 receptors may be up-regulated and display an inadequate ability to convert receptor occupancy by 5-HT into an adequate physiological response. Preclinical studies show that numerous antidepressants down-regulate both 5-HT1A and 5-HT2 receptors. Clinical studies using post mortem tissues, neuroendocrine probes, and platelet models also confirm that antidepressants down-regulate 5-HT receptors in depressed patients. In some cases this down-regulation correlates with measures of clinical antidepressant responsiveness. This correlation supports the hypothesis that down-regulation of 5-HT receptors, particularly the 1A and 2 subtypes, may be linked to the mechanism of action of numerous antidepressant drugs.
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PMID:5HT1A receptors and pharmacotherapy. Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs? 797 28

Thirty-three years ago, Gaddum and Picarelli classified the serotonin (5-HT) receptors in the guinea-pig ileum into D and M types based on the activity of dibenzyline (D) and morphine (M) to block contractions of intestinal smooth muscles caused by 5-HT. The subsequent location of specific ligand binding sites for 5-HT in the brain has led to the identification of 10 5-HT receptor subtypes in rat brain. While there is some controversy over the functional importance of many of these receptor subtypes, there is evidence that they fall into two major groups according to the nature of their coupling to secondary messengers or ion channels. Thus the 5-HT1 and 5-HT2 receptors appear to occupy the G protein receptor subfamily which may be coupled either to adenylate cyclase (most 5-HT1 subtypes) or phosphatidyl inositol (5-HT2 subtypes). The central "M" receptors (now termed 5-HT3) appear to occupy a ligand-gated ion channel superfamily. The cloning of these receptor subtypes has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. A problem now arises with regard to the linking of the changes in the cellular activity of the various receptor subtypes with the plethora of behavioural changes that arise as a consequence of the actions of 5-HT in the brain. The present review summarizes the evidence implicating the role of specific 5-HT receptor subtypes in thermoregulation, modulation of cardiovascular function, eating disorders, sleep, sexual activity, anxiety states, aggression, schizophrenia and depression. A summary of the relationship between these receptor subtypes and their possible involvement in the aetiology of these diseases is also given.
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PMID:Serotonin receptors--where are they going? 802 39

The effects of chronic administration of desipramine, citalopram, and electroconvulsive shocks (ECS) on changes in rat motility after intraaccumbens (NAS) injections of selective serotonergic drugs were studied in intact and 5.7-DHT lesioned animals. It was shown that local injections of 8-OHDPAT and DOI-HCl depressed rat locomotor activity. Their effects appeared to be mediated postsynaptically, and could be antagonized by NAN-190 and ritanserin, respectively. Chronic but not acute pretreatment of rats with antidepressants (21 days long; the experiment was performed 24 h after the last dose) as well as repeated ECS (shocks were applied five times every second day), antagonized behavioral depression after 8-OHDPAT and DOI-HCl. The influence of antidepressant treatment was prevented by serotonergic lesions. Chronic administration of antidepressants and ECS did not equivocally affect the levels or metabolism of 5-HT, dopamine, and noradrenaline in the rat limbic forebrain. It is concluded that the present data indicate diminished activity of 5-HT systems related to the 5-HT1A and 5-HT2 receptors in the limbic nucleus, after chronic antidepressant treatment. This effect of drugs and ECS concerns nervous processes linked with the function of postsynaptically localized 5-HT receptor subtypes, and it probably depends on intact presynaptic 5-HT innervation.
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PMID:Antidepressant treatment and limbic serotonergic mechanisms regulating rat locomotor activity. 809 Jul 97

The neuromodulator serotonin (5-hydroxytryptamine, 5-HT) has been associated with mood disorders such as depression, anxiety, and impulsive violence. To define the contribution of 5-HT receptor subtypes to behavior, mutant mice lacking the 5-HT1B receptor were generated by homologous recombination. These mice did not exhibit any obvious developmental or behavioral defects. However, the hyperlocomotor effect of the 5-HT1A/1B agonist RU24969 was absent in mutant mice, indicating that this effect is mediated by 5-HT1B receptors. Moreover, when confronted with an intruder, mutant mice attacked the intruder faster and more intensely than did wild-type mice, suggesting the participation of 5-HT1B receptors in aggressive behavior.
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PMID:Enhanced aggressive behavior in mice lacking 5-HT1B receptor. 809 Dec 14

Long-term exercise is associated with an antidepressant effect in patients with mild to moderate forms of nonbipolar depression and appears to be a promising new approach to its treatment. Adaptive changes in serotonin (5-HT) receptor functioning appears to play an important role in mediating the action of various antidepressant treatments. We investigated the adaptive changes in behavioral sensitivity of the 5-HT receptor subtype following 4 weeks of swimming exercise in normal rats, as well as in an animal model of depression (3 week, variety of chronic stressors). 5-HT1A autoreceptor sensitivity was assessed by hyperphagic response induced by 8-OH-DPAT (0.25 mg/kg, IP); 5-HT1A postsynaptic receptor by 5-HT syndrome induced by 8-OH-DPAT (0.75 mg/kg, IP), and 5 Me-ODMT (5 mg/kg, IP); and 5-HT2 receptor by wet dog shakes response induced by quipazine (1 mg/kg, IP) and 5MeODMT (5 mg/kg, IP). It was observed that exercise training in normal rats resulted in enhanced sensitivity of the 5-HT2 receptors along with subsensitivity of 5-HT1A autoreceptors. Exercise, given prophylactically along with chronic stressors, was able to prevent the development of behavioral deficit in the open-field test, and the animals developed remarkably enhanced sensitivity of 5-HT2 receptors. This adaptive supersensitivity of 5-HT2 receptor is also seen after various antidepressant treatments and may play an important role in mediating the antidepressant action of exercise.
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PMID:Physical exercise as a novel antidepressant agent: possible role of serotonin receptor subtypes. 815 73

Selective serotonin reuptake inhibitors (SSRIs) are effective in alleviating the symptoms of depression. However, clinical improvement is only obtained after several weeks of treatment. SSRIs, when administered acutely to animals, have little effect on synaptic levels of serotonin. This suggests the existence of one or more regulatory mechanisms controlling serotonergic neurotransmission. The firing rate of dorsal raphe serotonergic neurons is under the control of somatodendritic 5-hydroxytryptamine 1A (5-HT1A) autoreceptors, the release of serotonin from nerve terminals is under the control of 5-HT autoreceptors (5-HT1B subtype in rodents, 5-HT1D in other species), whereas the control of the activity of tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis, is complex, involving 5-HT1A but possibly other 5-HT receptors including the 5-HT1B/D subtype. During prolonged administration with a SSRI, these three feedback systems become desensitized and their regulatory effects on serotonergic neurotransmission are weakened or lost. This has the effect of allowing the synaptic levels of serotonin to rise with a consequently increased stimulation of one or more types of postsynaptic 5-HT receptor. Thus, it is only after prolonged administration that the pharmacological activity of SSRI is fully expressed in terms of synaptic serotonin levels. This may explain the latency of antidepressant action seen with these drugs in humans. Various other classes of antidepressant therapies (tricyclic antidepressants and monoamine oxidase inhibitor drugs, electroconvulsive therapy) have long-term effects on one or more of the feedback mechanisms such that an increase in synaptic concentrations of serotonin may be a common mechanism of many antidepressant therapies.
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PMID:Neurobiological mechanisms involved in antidepressant therapies. 822 1


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