کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4328040 | 1614154 | 2009 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: α1A- and α1B-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse α1A- and α1B-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse](/preview/png/4328040.png)
Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive–compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of α1-adrenergic receptors (α1-ARs). Yet, it is unclear whether increased α1-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant α1A-ARs (CAM α1A-AR) or CAM α1B-ARs were used to examine the effects of α1A- and α1B-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM α1A-AR mice, but not CAM α1B-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective α1-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an α1A-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM α1A-AR mice but not in CAM α1B-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM α1A-AR, and CAM α1B-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that α1A- and α1B-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that α1A-ARs may be a useful therapeutic target for the treatment of depression.
Journal: Brain Research - Volume 1285, 18 August 2009, Pages 148–157