RGD Reference Report - alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse. - Rat Genome Database

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alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.

Authors: Doze, VA  Handel, EM  Jensen, KA  Darsie, B  Luger, EJ  Haselton, JR  Talbot, JN  Rorabaugh, BR 
Citation: Doze VA, etal., Brain Res. 2009 Aug 18;1285:148-57. Epub 2009 Jun 18.
RGD ID: 5688369
Pubmed: PMID:19540213   (View Abstract at PubMed)
PMCID: PMC2720445   (View Article at PubMed Central)
DOI: DOI:10.1016/j.brainres.2009.06.035   (Journal Full-text)

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 alpha(1)-adrenergic receptors (alpha(1)-ARs). Yet, it is unclear whether increased alpha(1)-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 alpha(1A)-ARs (CAM alpha(1A)-AR) or CAM alpha(1B)-ARs were used to examine the effects of alpha(1A)- and alpha(1B)-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM alpha(1A)-AR mice, but not CAM alpha(1B)-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective alpha(1)-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an alpha(1A)-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM alpha(1A)-AR mice but not in CAM alpha(1B)-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM alpha(1A)-AR, and CAM alpha(1B)-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that alpha(1A)- and alpha(1B)-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that alpha(1A)-ARs may be a useful therapeutic target for the treatment of depression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
depressive disorder  ISOAdra1a (Mus musculus)5688369; 5688369 RGD 
depressive disorder  IDA 5688369 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adra1a  (adrenoceptor alpha 1A)

Genes (Mus musculus)
Adra1a  (adrenergic receptor, alpha 1a)

Genes (Homo sapiens)
ADRA1A  (adrenoceptor alpha 1A)


Additional Information