%0 Journal Article %A Van A. Doze %A Robert S. Papay %A Brianna L. Goldenstein %A Manveen K. Gupta %A Katie M. Collette %A Brian W. Nelson %A Mariaha J. Lyons %A Bethany A. Davis %A Elizabeth J. Luger %A Sarah G. Wood %A James R. Haselton %A Paul C. Simpson %A Dianne M. Perez %T Long-Term α1A-Adrenergic Receptor Stimulation Improves Synaptic Plasticity, Cognitive Function, Mood, and Longevity %D 2011 %R 10.1124/mol.111.073734 %J Molecular Pharmacology %P 747-758 %V 80 %N 4 %X The role of α1-adrenergic receptors (α1ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. α1AAR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term α1AAR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the α1AAR. CAM-α1AAR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the α1AAR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-α1AAR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the α1AAR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-α1AAR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-α1AAR mice was 10% longer than that of WT mice. Our results suggest that long-term α1AAR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders. %U https://molpharm.aspetjournals.org/content/molpharm/80/4/747.full.pdf