Chapters authored
Association of 5-HT1A Receptors with Affective Disorders
Serotonin or 5-hydroxytryptamine (5-HT) is synthesized in both the brain and peripheral system, which exert their actions at a wide family of receptors classified as 5-HT1 to 5-HT7. Pharmacological, behavioral, and clinical studies involve particularly to the 5-HT1A receptors (5-HT1A-R) - auto-receptors (presynaptic) and heteroreceptors (postsynaptic) - in the control of motivated behavior, and consequently in the physiopathology of affective disorders and in the action mechanism of antidepressant drugs. In this way, some research support that 5-HT1A-R participates in the delayed effect of different types of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), and tricyclic drugs, principally. The therapeutic effect of serotonergic drugs as the SSRIs, starting with the binding to auto-receptors, which produces increases of 5-HT in the synaptic cleft as consequence of blockade of serotonin reuptake. While these molecular events occur initially, in the long-term are produced plastic changes at neuronal level, as well as down-regulation of the 5-HT1A-R, which is associated with the therapeutic effects of antidepressant drugs. The purpose of this chapter is to analyze and discuss the current information about of 5-HT1A-R-mediated signaling cascades, the intracellular signaling of 5-HT1A-R, in addition to their expression and pharmacology that are important to treatment of affective disorders symptoms.
Part of the book: Serotonin
Depression and Serotonergic Changes during the Climacteric and Postmenopausal Stages: Hormonal Influences
Depression is a psychiatric disorder that affects a high percentage of women. Most of the depression disorders turn up during the premenopause and perimenopause stages when the hormonal oscillations make an impact in the brain function principally on the serotonergic system, which is related to neurobiology of depression. 5-HT1A and 5-HT2A receptors change on functionality and density in afferent areas related to emotional modulation and increased serotonin clearance, and the binding potential of serotonin transport has been related to the underlying mechanism of the depression during the climacteric or postmenopausal stage. Some findings have been proven on preclinical studies. These studies on animals have recognized how estrogen treatment activates intracellular signaling pathways as mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK), tyrosine kinase brain-derived neurotrophic factor receptor (TrKB), insulin-like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3)/serine/threonine-specific protein kinase (Akt), and metabotropic glutamate receptor 1 (mGluR1) which interact with the serotonergic system to allow establishment of the estradiol effects on mood regulation. Thus, the interaction between the woman’s reproductive status and the serotonin changes could be useful to create prevention strategies, early diagnosis, and medical treatment of climacteric and postmenopausal women with depression, in order to improve their quality of life.
Part of the book: Menopause