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Neurobiology of Monoaminergic Neurotransmission and Antidepressants

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Melatonin and Melatonergic Drugs in Clinical Practice

Abstract

Pathophysiological mechanisms underlying depression are complex and are at multiple levels of analysis. But, during the 1960s, monoamine theories of depression flourished, postulating that a fundamental cause of depression was a functional deficit in noradrenergic and serotonergic neurotransmission in certain areas of the brain. These hypotheses were developed based on the fact that certain drugs that lessened depressive symptoms had monoaminergic properties, like blocking the serotonin transporter (5-HTT) or inhibiting MAO enzymes. Thus, any sort of alteration in monoamine functioning, whether in its synthesis, storage, release, or biotransformation, not to mention changes in its reuptake or monoamine receptor sensitivity, was related to the manifestation of characteristic depressive and behavioral symptoms (e.g., mood, alertness, motivation, fatigue, agitation, and psychomotor retardation).

It is generally accepted that a variety of genetic, environmental, and neurobiological factors are implicated in depression. The 5-HTT gene (SLC6A4) and other genes involved in the serotonergic system (polymorphisms on TPH2, 5-HT1A or COMT genes), norepinephrine transporter (NET, SLC6A2), and dopamine transporter (DAT, SLC6A) are candidates for susceptibility to depression. Many antidepressant medications act on that system. This chapter analyzes the validity of the monoamine hypothesis of depression, its intersections with other neurobiological mechanisms, and antidepressants’ influence on such mechanisms. The monoamine hypothesis of depression is critically discussed. Specifically, we wish to add to the body of knowledge about monoamines in the pathophysiology of depression and to suggest other neurobiological aspects that could help improve the treatment of such disorders.

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Authors and Affiliations

  1. Faculty of Health Sciences, Camilo José Cela University and Hospital 12 de Octubre Research Institute, C/Castillo de Alarcón, 49, Urb. Villafranca del Castillo, Villanueva de la Cañada, Madrid, 28692, Spain

    Francisco López-Muñoz MD, PhD

  2. Department of Pharmacology, Faculty of Medicine, University of Alcalá, Serrano Galvache 42, 9ºC., Madrid, 28033, Spain

    Cecilio Álamo MD, PhD

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  1. Francisco López-Muñoz MD, PhD
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  2. Cecilio Álamo MD, PhD
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Correspondence to Francisco López-Muñoz MD, PhD .

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  1. Sri Sathya Sai Medical Educational and Research Foundation, An International Medical Sciences Research Center, Coimbatore, Tamil Nadu, India

    V. Srinivasan

  2. Department of Obstetrics and Gynecology, Hadassah Hebrew-University Medical Center, Jerusalem, Israel

    Amnon Brzezinski

  3. Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey

    Sukru Oter

  4. Department of Psychiatry Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA

    Samuel D. Shillcutt

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López-Muñoz, F., Álamo, C. (2014). Neurobiology of Monoaminergic Neurotransmission and Antidepressants. In: Srinivasan, V., Brzezinski, A., Oter, S., Shillcutt, S. (eds) Melatonin and Melatonergic Drugs in Clinical Practice. Springer, New Delhi. https://doi.org/10.1007/978-81-322-0825-9_23

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  • DOI: https://doi.org/10.1007/978-81-322-0825-9_23

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  • Online ISBN: 978-81-322-0825-9

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