Alpha1A Adrenergic Receptor Stimulation Improves Mood in Mice

Abstract

The role of alpha1‐adrenergic receptors (alpha1‐ARs) in cognition and mood is controversial, likely due to past use of non‐selective agents. Activation of the alpha1A‐AR subtype was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of chronic alpha1A‐AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM). Previously, we found that CAM‐alpha1A‐AR mice demonstrated enhancements in several behavioral models of learning and memory. We now report that CAM‐alpha1A‐AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests when compared to normal wild‐type littermate control mice. Furthermore, the reduction in anxiety‐ and depressive‐like behaviors was present in both sexes and across all ages (young to old). Our results suggest that chronic alpha1A‐AR stimulation improves cognitive function and mood. These results suggest that long‐term alpha1A‐AR stimulation may afford a potential therapeutic target for treating anxiety and depression. This strategy may also be effective in counteracting the decline in cognitive function and mood associated with aging and neurological disorders. This study was supported in part by NSF CAREER Award 0347259, NSF REU Site Grant 0851869, UNDSMHS REFUNDU program, NIH NCRR INBRE Grant P20RR016471, and NIH Grant RO1HL61438.