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

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

Author(s): B. M. Ruf and Z. Bhagwagar
Pages 1118-1138 (21)
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.
Serotonin receptor, serotonin, mood disorders, major depressive disorder, genetic polymorphism, antidepressive agents, S100 proteins, S100 calcium binding protein A10
Department of Psychiatry, Yale University, New Haven 06519, USA.