α1A - and α1B -adrenergic receptors differentially modulate antidepressant-like behavior in the mouse

• Published in: Brain research 2009-08, Vol.1285, p.148-157
• Main Authors: Doze, Van A, Handel, Evelyn M, Jensen, Kelly A, Darsie, Belle, Luger, Elizabeth J, Haselton, James R, Talbot, Jeffery N, Rorabaugh, Boyd R
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Depression; Medical sciences; Mood disorders; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.06.035

Abstract 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.