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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 10
ISSUE: 11
DOI: 10.2174/138945009789735192      Price:  $58









The 5-HT1B Receptor: A Novel Target for the Pathophysiology of Depression (Supplementary Tables)

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Author(s): B. M. Ruf and Z. Bhagwagar
Pages 1118-1138 (21)
Abstract:
The serotonergic (5-HT) system has been widely implicated in the pathophysiology of Major Depressive Disorder (MDD). Although the 5-HT system is a popular target for drug therapy in MDD, the role that serotonin plays in MDD is not clearly understood. An abundance of research suggests that several 5-HT receptor subtypes may be dysfunctional in patients with MDD including the 5-HT1B receptor. Evidence implicating 5-HT1B receptors in the pathophysiology of depression comes from a number of converging lines of research. Two common genetic polymorphisms of 5-HT1B receptors, G861C and C129T, have been implicated in affective disorders. Rats predisposed to learned helplessness have exhibited downregulation of 5-HT1B receptor messenger ribonucleic acid (mRNA) in dorsal raphe nucleus (DRN). Pharmacological studies have demonstrated augmentation of extracellular 5-HT levels and antidepressant effects following administration of selective serotonin reuptake inhibitors (SSRIs) in the absence or blockade of 5-HT1B receptors. 5-HT1B receptor agonists administered alone or with antidepressants have been shown to be effective in preclinical models of depression. Recent interest has focused on p11, an s100 EF-hand protein family protein which colocalizes with 5-HT1B receptors. P11 plays a central role in the modulation of 5-HT1B receptor function and is dysregulated in preclinical models of depression and postmortem MDD samples. A review of the literature provides strong evidence that 5-HT1B receptors and related factors such as p11 are involved in the pathophysiology of depression. The following explores possible factors which may render the 5-HT1B receptor dysfunctional, resulting in susceptibility to depression. Implications of using the 5- HT1B receptor as a biomarker for vulnerability to MDD are discussed.
Keywords:
Serotonin receptor, serotonin, mood disorders, major depressive disorder, genetic polymorphism, antidepressive agents, S100 proteins, S100 calcium binding protein A10
Affiliation:
Department of Psychiatry, Yale University, New Haven 06519, USA.