The functional serotonin 1a receptor

The functional serotonin 1a receptor
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Substantial evidence supports the role of serotonin 1a receptors (5-HT1A) in modulating anxiety and depression-related traits and impacting antidepressant efficacy.1 5-HT1A receptors are highly expressed in areas with strong involvement in emotional and affective processes, including the hippocampus, cingulate cortex, orbitofrontal cortex, insula, amygdala and midbrain raphe.2, 3 Positron emission tomography imaging studies have found altered 5-HT1A levels in major depressive disorder (MDD),4, 5, 6, 7, 8 bipolar disorder9 and anxiety disorders.10, 11, 12 Postmortem data also point toward altered 5-HT1A density in depression and suicide.13, 14, 15, 16, 17, 18 Clinically, the 5-HT1A partial agonist, buspirone, is used in the treatment of anxiety disorders19 and vilazodone with battery such as Agilent N9330 Battery, Agilent N9330B Battery, Agilent N9340B Battery, Agilent N9330B-BAT Battery, Agilent N9330B-BCG Battery, Agilent TY 3CGR18650D-2 Battery, IAI AV6413 Battery, Unipower B11588 Battery, Alpha Source AS30139 Battery, Interstate Batteries AMED2160, Interstate Batteries ACAM0300, Alpha Source AS36011 Battery, a partial 5-HT1A agonist and serotonin reuptake inhibitor, is used in the treatment of depression.20
Work in animal models has also highlighted the distinct behavioral contributions of 5-HT1A receptors across different brain regions and at different developmental time points.21 Pharmacological studies have indicated that postnatal but not adult administration of a 5-HT1A antagonist leads to increased anxiety later in life,22, 23 and genetic studies suggest that this effect is mediated by 5-HT1A autoreceptors localized on serotonergic neurons in the raphe.24, 25 In contrast, manipulations of 5-HT1A in the raphe selectively during adulthood has no effects on anxiety, but does impact stress-coping behaviors and antidepressant responsiveness.26 In the forebrain, whole-life suppression of 5-HT1A levels may affect depression-related behavior.27 Thus, the forebrain and midbrain 5-HT1A populations modulate distinct behaviors, and their contribution to behavior evolves across the course of development. Further, relatively small alterations in receptor levels are sufficient to impact behavior,24, 26 indicating that naturally occurring variation in receptor levels may contribute to individual differences in behavior. Given the multiple lines of evidence implicating variation in 5-HT1A levels in mental illness, there is a clear need to identify the factors that contribute to variation in 5-HT1A expression across the lifetime to guide individualized treatment and intervention.
Studies of the transcriptional regulation of the serotonin 1a receptor gene (HTR1A) have identified a putatively functional G/C single-nucleotide polymorphism (SNP) located 1019 bp upstream of the translation start site, designated rs6295.28 The G-allele of this SNP was initially found to be overrepresented in suicide,29 and was also associated with a decreased responsiveness to antidepressants.30 As with many gene associations, replications of these results have been inconsistent, but a series of recent meta-analyses supports an association between rs6295 and mood disorders, specifically MDD and bipolar disorder.31, 32, 33 In addition, this SNP has also been associated with a variety of other illnesses, including panic disorder,16 substance abuse,16 premenstrual dysphoric disorder,34, 35 eating disorders36 and schizophrenia16 (reviewed in ref. 28). These findings suggest that rs6295 may impact intermediate phenotypes that are common to multiple disorders.37