@article {Dozemol.111.073734, author = {Van A Doze and Robert S. Papay and Brianna L Goldenstein and Manveen K Gupta and Katie M Collette and Brian W Nelson and Mariaha J Lyons and Bethany A Davis and Elizabeth J Luger and Sarah G Wood and James R Haselton and Paul C. Simpson and Dianne M Perez}, title = {Chronic α1A-adrenergic Receptor Stimulation Improves Synaptic Plasticity, Cognitive Function, Mood, and Longevity}, elocation-id = {mol.111.073734}, year = {2011}, doi = {10.1124/mol.111.073734}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The role of α1-adrenergic receptors (α1ARs) in cognition and mood is controversial, likely due to past use of non-selective agents. α1AAR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of chronic α1AAR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM). CAM-α1AAR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the α1AAR gene knocked-out (KO) displayed poor cognitive function. Hippocampal brain slices from CAM-α1AAR mice showed displayed basal synaptic transmission, paired-pulse facilitation and long-term potentiation compared to 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 when compared to WT. Furthermore, the lifespan of CAM-α1AAR mice was 10 percent longer than that of WT mice. Our results suggest that chronic 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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2011/07/26/mol.111.073734}, eprint = {https://molpharm.aspetjournals.org/content/early/2011/07/26/mol.111.073734.full.pdf}, journal = {Molecular Pharmacology} }