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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The past decade has seen important progress in understanding the localization, pharmacology, and function of serotonin (5-HT) receptor subtypes. At least seven subclasses have been shown to exist, and evidence is emerging to suggest further subclassification. Serotonin is involved in numerous physiological processes (e.g. feeding, sleep, pain, sexual behavior, temperature regulation) and pathophysiological ones. Serotonin reuptake blockers have been found effective in the alleviation of depression and attacks of panic, and are at varying stages of clinical evaluation in the treatment of obsessive compulsive disorder, chronic pain, and bulimia nervosa. Selective potent serotonin receptor agonists and antagonists show promise in the treatment of migraine, nausea and vomiting, schizophrenia, anxiety, hypertension, and Raynaud's disease.
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PMID:[New therapeutic possibilities with drugs affecting serotonin receptors]. 150 27

Thirty-three years ago, Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline and morphine to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of at least eight serotonin receptor sub-types in rat brain. While there is some controversy over the functional importance of many of these receptor sub-types, 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 sub-family which may be coupled either to adenylate cyclase (most 5-HT1 sub-types) or phosphatidyl inositol (5-HT2 sub-types). The central "M" receptors (now termed 5-HT3) appear to occupy a ligand gated ion channel super-family. The cloning of three of the serotonin receptor sub-types in 1989 (5-HT1A, 5-HT1C and 5-HT2) has been of importance in enabling the receptor sub-types to be classified as specific protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in eating disorders, sleep, sexual activity, anxiety states, aggression, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the aetiology of these diseases is shown in Table 2.
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PMID:Sub-types of serotonin receptors: biochemical changes and pharmacological consequences. 162 53

The classical neurotransmitters serotonin and dopamine are thought to be involved in the etiology or treatment of a variety of psychiatric disorders. Recent studies suggest that these neurotransmitters may also have roles as neural morphogens during brain development. Previously, we have demonstrated that stimulation of serotonin 5-HT1A receptors selectively inhibited neurite branching in an in vitro system (Sikich et al 1990). In the present study, the developmental role of dopamine D2 receptors in the control of neurite outgrowth has been investigated by quantitating the morphological response of cortical neurons to agonist stimulation in vitro. Cultures of fetal rat frontal, cortical neurons were shown to express both alternatively spliced forms of D2 receptor messenger RNA (mRNA). The larger mRNA form predominated (D2A444:D2A415 ratio of about 6:1). In a small but significant percentage of these neurons, culture in the presence of the D2 receptor selective agonist, quinpirole, resulted in a three-to ten-fold increase in the length of neurites and in the number of branch points per neurite. These effects were blocked by the D2 receptor antagonists eticlopride and spiperone. Early abnormalities in the stimulation of dopamine or serotonin receptor subtypes could lead to the types of neuroanatomical changes observed in studies of schizophrenia, bipolar affective disorder, and autism. These morphogenic effects of classical transmitters could unite neurodevelopmental and neurotransmitter theories of the etiology of severe psychiatric disorders.
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PMID:Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. 164 94

Several developments in serotonin neuropharmacology have implications for psychiatric disorders and have already begun to impact their treatment. Selective inhibitors of serotonin uptake, which enhance serotonergic function by preventing the removal of serotonin from the synaptic cleft via the membrane transporter, have been introduced for the treatment of depression and may be effective in other disorders. Precursor loading can increase serotonin concentrations in the synaptic cleft, and tryptophan--which has been available in health food stores and drug stores--had become increasingly used for self-medication of depression, insomnia, and premenstrual syndrome. Conversion to serotonin is not the major metabolic pathway for tryptophan, and large increases in other tryptophan metabolites (such as quinolinic acid, a substance that is excitotoxic at high concentrations) accompany small increases in extracellular serotonin. The recent epidemic of the eosinophilia-myalgia syndrome associated with tryptophan now appears due to a trace contaminant in the product from a single manufacturer. A major advance in serotonin pharmacology has been the elucidation of serotonin receptor heterogeneity. At least seven receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, 5-HT3, 5-HT4) have been identified in brain. Direct-acting agonists and antagonists can have selective affinity for specific receptor subtypes. Selective activation of 5-HT1A receptors seems to cause anxiolytic and possibly antidepressive effects. Selective antagonists of 5-HT2 or 5-HT3 receptors may be useful in treating anxiety and schizophrenia. Drugs that enhance serotonergic function suppress aggression in animals, but the specific receptor subtypes involved are not known. The advances being made in serotonin pharmacology will help define the role of this brain neurotransmitter in psychiatric and other disorders and can be expected to lead to further therapeutic advances.
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PMID:Role of serotonin in therapy of depression and related disorders. 167 51

The nonpathological age-related changes in the dopamine- and serotonin-containing neurotransmitter systems in human and rodent brain are reviewed. The dopamine system exhibits age-related declines both presynaptically and postsynaptically. Presynaptically, both the levels of dopamine and the number of midbrain dopamine-containing neurons decline by up to 50% at advanced ages in the absence of neurological disease. Postsynaptically, the density of D-2 dopamine receptors decreases by 40%, while D-1 dopamine receptors either increase (man) or remain stable (rodents). Additional reductions of dopamine levels and D-2 receptors have been reported in Alzheimer's disease (AD), but these changes are relatively small, and not consistently observed. The levels of serotonin appear stable during normal aging, and presynaptic markers such as (3H)imipramine binding may actually increase. In human brain, the two major classes of serotonin receptor (S-1 and S-2) decrease by 30 to 50% over the lifespan. In AD, both presynaptic and postsynaptic markers of the serotonin system are reduced, including a loss of the serotonin-containing raphe neurons. The additional loss of serotonin receptors in AD approaches 80% when compared with young normals. A hypothesis is presented to explain the typically young age at onset of schizophrenia (usually before 30 years of age) and the older age at onset of parkinsonism (rarely before 50 years of age) within the context of normal age-related declines in the dopamine system occurring in the absence of neurological disorders. The possibility that chronic cocaine abuse might accelerate the development of parkinsonism is discussed.
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PMID:Dopamine and serotonin systems in human and rodent brain: effects of age and neurodegenerative disease. 354 45

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

Serotonin is a neurotransmitter that is widely distributed throughout the central nervous system. The role of serotonin in schizophrenia is still unclear. Postmortem studies of serotonin receptor subtypes in schizophrenia have been inconclusive for the most part. The most promising findings involve a reduction in 5-HT2 receptors and 5-HT reuptake sites in the prefrontal cortex of schizophrenic patients. In this paper we review the function, distribution and pharmacological characteristics of serotonin receptors. Postmortem studies are also reviewed, focusing upon the role of these receptors in schizophrenia.
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PMID:The role of serotonin in schizophrenia: an overview of the nomenclature, distribution and alterations of serotonin receptors in the central nervous system. 783 40

Alterations in density of some serotonin receptor sites (5-HT1A receptors, 5-HT2 receptors and 5-HT uptake sites) have been reported in postmortem studies of brain obtained from subjects with schizophrenia, suggesting a disturbance in serotonergic transmission in schizophrenia. The purpose of the present study is to investigate [3H]-LY278584 binding to serotonin 5-HT3 receptors in postmortem samples of amygdala from schizophrenic and matched control subjects. As all of the schizophrenic patients but none of the controls had been treated with neuroleptics, we first investigated in rodents the effects of short-term and long-term haloperidol administration on limbic 5-HT3 receptors, and we found no effects. No differences in the maximum number of 5-HT3 binding sites (Bmax) or equilibrium dissociation constant (Kd) between schizophrenics and controls were found in amygdala. This study does not support the presence of an alteration of 5-HT3 receptors in amygdala in schizophrenic patients.
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PMID:Serotonin 5-HT3 receptors in schizophrenia: a postmortem study of the amygdala. 835 29

Sixty-two patients with schizophrenia and 96 normal controls were investigated for genetic association with restriction fragment length polymorphisms (RFLPs) in the serotonin receptor genes. A positive association between the serotonin 2A receptor gene (HTR2A) and schizophrenia was found, but not between schizophrenia and the serotonin 1A receptor gene. The positive association we report here would suggest that the DNA region with susceptibility to schizophrenia lies in the HTR2A on the long arm of chromosomes 13.
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PMID:Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia. 867 5

Thirty-three years ago, Gaddum and Picarelli classified the serotonin 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 muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of 14 serotonin receptor sub-types in rat brain. The cloning of these receptor sub-types has been of importance in enabling them to be classified as specific-protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in sleep, anxiety states, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the aetiology of schizophrenia, depression, anxiety and sleep disorders.
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PMID:Serotonin receptors and their function in sleep, anxiety disorders and depression. 871 Oct 84


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