Serotonin Research

6 Key excerpts on "Serotonin Research"

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  eBook - ePub

  Compendium Of In Vivo Monitoring In Real-time Molecular Neuroscience - Volume 1: Fundamentals And Applications

  Volume 1: Fundamentals and Applications

  • George S Wilson, Adrian C Michael(Authors)
  • 2014(Publication Date)
  • WSPC

    (Publisher)

  CHAPTER 12 PROBING SEROTONIN NEUROTRANSMISSION: IMPLICATIONS FOR NEUROPSYCHIATRIC DISORDERS Kevin M. Wood, David Cepeda and Parastoo Hashemi Wayne State University 12.1 INTRODUCTION

  Serotonin is a unique neurotransmitter. About 98% of the body’s serotonin is located outside of the brain (Cooper et al., 2003), however, as a neuromodulator it plays important, expansive roles. Serotonin is thought to control many essential processes including appetite, sleep, mood, memory, cognition, movement and reward. Imbalances in the serotonergic system are associated with many neuropsychiatric disorders.

  Autism (Chugani et al., 1997; Sutcliffe et al., 2005), post-traumatic stress disorder (PTSD) (Lee et al., 2005), anxiety (Lesch et al., 1996; Sen et al., 2004; Ramboz et al., 1998), schizophrenia (Inayama et al., 1996; Laruelle et al., 1993), bipolar disorder (Furlong et al., 1998; Young et al., 1994), and addiction (Muller et al. 2007; Sellers et al., 1992) all display distinct deregulations of the serotonergic system.

  The most notorious of serotonin’s associations, however, is depression. Depression debilitates millions of Americans every year; it is a mental illness that can destroy feelings of joy gained from previous exciting activities. Fatigue, hopelessness, irritability, and excessive sadness can plague the sufferer. In 2011, antidepressants and antipsychotics dominated the pharmaceutical market (Lindsley, 2012).

  Modern antidepressants typically exaggerate serotonin’s effects in the synapse by slowing down its reuptake. Despite their mainstream usage, antidepressants generate controversy because of variable clinical efficacy (Smith et al., 2002; Cipriani et al., 2009) and systemic side effects (Ferguson, 2001; Masand and Gupta, 2002). Moreover, it is common for patients to take antidepressants for 3–4 weeks without experiencing therapeutic benefit (Gelenberg and Chesen, 2000; Onder and Tural, 2003). During this period patients can experience heightened depression and suicidal tendencies (Stone et al., 2009).

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  Serotonin

  • Ying Qu(Author)
  • 2019(Publication Date)
  • IntechOpen

    (Publisher)

  1 Chapter 1 Introductory Chapter: From Measuring Serotonin Neurotransmission to Evaluating Serotonin Post-Receptor Signaling Transduction Ying Qu 1. Introduction Serotonin or 5-hydroxytryptamine (5-HT) is a well-established monoamine neurotransmitter in the central nervous system (CNS). The discovery of 5-HT dates as far back as 1868 and can be traced to its presence in the blood and in the gastrointesti-nal tract [1]. Its well-known biological functions include modulating cognition, sleep, emotion, learning, memory, and numerous physiological processes. 5-HT is primarily found in the enteric nervous system located in the gastrointestinal tract [2], where it Figure 1. Model explaining PLA 2 activation in response to serotonergic drugs. Under normal conditions, the 5-HT that is released from presynaptic vesicles into the synaptic cleft binds to postsynaptic 5-HT receptors coupled via a G-protein to PLA 2 , thus hydrolyzing arachidonic acid (AA) from membrane phospholipids (PL). Administration serotonergic drugs activate PLA and increase incorporation of AA by different routes. (1) 5-HT 2A/2C agonist, DOI directly binds to 5-HT 2 receptors to activate this signal; (2) fluoxetine (SSRI) inhibits 5-HT uptake, thus increasing 5-HT in the synaptic cleft so as to increase PLA activation and AA release. This figure adapted from [23]. Serotonin 2 regulates intestinal movements [2], and the remainder is synthesized in the serotoner-gic neurons of the CNS, where it has various functions such as the regulation of mood, appetite, and sleep. Modulation of 5-HT at synapses is thought to be a major action of several classes of pharmacological antidepressants. Among these, selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and citalopram, are the most important class of antidepressant in the treatment of major depressive disorder (MDD) and anxi-ety disorders [3]. The exact mechanism of action of SSRIs is not fully revealed.

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  Neurobiology of Depression

  • Francisco Lopez-Munoz, Cecilio Alamo(Authors)
  • 2011(Publication Date)
  • CRC Press

    (Publisher)

  Recently, serotonin neurons have been classified based on genetic lineages. Specifically, sero-tonin neuronal progenitors can be subdivided into subsets defined by rhombomeres (r1, r2, r3, r5), which are discriminated by differing genetic cues (transcription factors) during development (Jensen et al. 2008). The broad functions of serotonin in the central nervous system include its involvement in the modulation of aggression, sleep, appetite, mood, thermoregulation, and sexual function; however, serotonin levels in the brain account for only 10% of the total serotonin in the body (Berger et al. 2009). In the periphery, serotonin is predominantly found in enterochromaffin cells of the gut, where it functions in smooth muscle contraction and gut motility (Spiller 2008). Additionally, sero-tonin is taken up into platelets, where it is released to cause vasoconstriction and is involved in cardiovascular regulation (Ramage and Villalon 2008). Serotonin is also found in lymphocytes and monocytes and is associated with immune system function (Gordon and Barnes 2003). Peripheral tissues express SERT and multiple serotonin receptors, and thus possess many of the components of the central serotonin system (Berger et al. 2009). As will be discussed later, correlations between central and peripheral serotonin system components are important for advances in depression research, whereby peripheral cells might be used as diagnostic tools to study treatment responses in cases where direct brain measurements are not feasible. 7.3 THE MONOAMINE HYPOTHESIS OF DEPRESSION 7.3.1 D ISCOVERY OF THE R OLE OF S EROTONIN Early evidence for the involvement of monoamine neurotransmitters, including serotonin, in depres-sion and other affective disorders arose serendipitously. Reserpine ( Rauwolfia serpentina ) was first used as an ayurvedic treatment for insanity, producing calming effects and lowering blood pres-sure (Sen and Bose 1931; Gupta et al. 1947; Vakil 1949).

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  Stress: Physiology, Biochemistry, and Pathology

  Handbook of Stress Series, Volume 3

  • George Fink(Author)
  • 2019(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 10

  Serotonin in Stress

  Maarten van den Buuse, and Matthew W. Hale     School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia

  Abstract

  Serotonin is implicated in the pathology of several psychiatric disorder, including major depression, general anxiety disorder, posttraumatic stress disorder, and schizophrenia. Stress plays a role in all these diseases, either as a causative factor or to exacerbate symptoms. Stress affects several aspects of serotonergic signaling in the brain and, conversely, serotonergic drugs can modulate the effects of stress. This chapter will summarize the complex and reciprocal interrelationship between stress and brain serotonin signaling with a focus on psychiatric disorder. The literature shows that stress effects on the serotonin system are regionally different throughout the brain and are dependent on the type of stress, its duration, the serotonergic marker measured, and individual differences in resilience and genetic background.

  Keywords

  5-HT1A receptor; Depression; Glucocorticoid receptors; Hippocampus; PTSD; Raphe nucleus; Schizophrenia; Serotonin; Serotonin transporter polymorphism

  Outline

  1. Introduction: Stress, Serotonin, and Human Psychopathology 
  2. Effect of Stress on Serotonin Parameters in the Brain 
     1. Animal Models 
     2. Human Imaging 
  3. Effect of Serotonergic Drugs on Stress Responses: Serotonin and HPA Axis Activity 
     1. Animal Models 
     2. Human Studies 
  4. Stress, Serotonin, and Human Psychopathology 
     1. Anxiety, PTSD, and Depression 
     2. Psychoses 
  5. Conclusions 
  6. References 

  Introduction: Stress, Serotonin, and Human Psychopathology

  It is widely accepted that stress plays a role in the pathology of several psychiatric disorders. This is most notable in mood and anxiety disorders such as major depression, general anxiety disorder, and posttraumatic stress disorder (PTSD) but, similarly, stress has been shown to play a role or exacerbate symptoms in psychotic illnesses, such as schizophrenia (Fig. 10.1 , ➀). Serotonin systems in the brain are implicated in all these disorders (Fig. 10.1 , ➁). There is a wealth of literature showing that stress affects serotonergic signaling in the brain (Fig. 10.1 , ➂) and thereby influences disease development. Conversely, serotonergic drugs can modulate or mitigate the effects of stress in psychopathology (Fig. 10.1

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  The Greening of Pharmaceutical Engineering, Applications for Mental Disorder Treatments

  • M. R. Islam, Jaan S. Islam, Gary M. Zatzman(Authors)
  • 2017(Publication Date)
  • Wiley-Scrivener

    (Publisher)

  Instead of developing a newer version of SSRIs and hoping for the best (once again), it’s time to make fundamental changes in the ways we address mental health disorders. 3.4 Something ‘Left’ to Say About Serotonin Serotonin is one of several neurotransmitters in our body. Like all neu-rotransmitters, it has several function and effects. One of its major effects is to regulate intestinal movements, for which approximately 90% of it is used (Oh, 2014). It also participates in hypothalamic control of pituitary hor-mone secretion, and participates in the biological clock of a person (Frazer and Hensler, 1999), memory, mood emotions, and appetite (Jonnakuty, 2008). There are several functions and effects of serotonin increase or decrease, or reuptake inhibition. Effects can be very complex, and we know for sure that there is very little information and fact on the subject. Anyone can take a quick look at the side effects, post-marketing research, and hundreds of papers discussing several effects of serotonin on the body; new ones are coming out every day, and they are all contradictory, creating paradoxes. The bottom line is, new science has little idea how complex the human body is and how specific neurotransmitters and biological regula-tors affect the body. We are newly discovering how else serotonin affects the body. In 2011, a researcher of bone biology at Columbia University (who found links of serotonin on the bones) said, “If I didn’t admit to being surprised by the scope of serotonin function, and important it is to tissues like bone, I would be lying” (quote reported by Angier, 2011). 18 This is the reason why Saint John’s wort works but chemical drugs don’t. 122 The Greening of Pharmaceutical Engineering There are several effects we know of, and more likely hundreds if not thousands of effects we still don’t know about. So far, we are only able to identify about 15 serotonin receptors (See “McGill the Brain”, website 4 in References).

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  Serotonin and Behavior

  • Jack Barchas(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  The second approach involves the utilization of primate models for the study of psychiatric disorders. In an earlier session, papers were presented dealing with the effects of an inhibitor of serotonin formation on behavior in groups of monkeys. The use of primate models, such as separation, might provide means of determining the effects of altering amines in relation to the behavioral changes. Such studies could provide data that could potentially be useful clinically.

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  ROLE OF SEROTONIN IN AFFECTIVE DISORDERS

  A. Coppen

  Publisher Summary

  This chapter discusses the role of serotonin in affective disorders. The investigation of the biochemistry of the affective disorders and mental illness in general presents a variety of difficult and apparently often insuperable problems. There is evidence of a disturbance of 5-hydroxytryptamine in the central nervous system of depressive and manic patients. The evidence suggests that clinical recovery is not accompanied by any change in this abnormality and therefore, it is a predisposition that requires another factor to produce the clinical picture of depression and mania. However, measures to increase amines, especially 5-hydroxytryptamine, by administering large doses of tryptophan and monoamine oxidase inhibition is an effective antidepressant treatment, and it is, therefore, probable that the change in amines has a direct relationship with some of the symptoms of a depressive illness.

  The investigation of the biochemistry of the affective disorders and mental illness in general presents a variety of difficult and apparently often insuperable problems. The absence of any convincing animal model for depression and mania compels the investigator to turn to experimentation on patients. These investigations present a wealth of ethical, practical and theoretical problems. For example, it is extremely difficult to get any information about processes in the brain, in vivo , in man – yet, presumably, it is this organ that is concerned in the aetiology of mental illness. The nearest one can get to the central nervous system, in practice, is the lumbar cerebrospinal fluid, although recent studies (Bulat and Zivkovic, 1971

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