The role of α(1)-adrenergic receptors (α(1)ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. α(1A)AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood.
We studied the effects of long-term α(1A)AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the α(1A)AR. CAM-α(1A)AR mice showed enhancements in several behavioral models of learning and memory.
In contrast, mice that have the α(1A)AR gene knocked out displayed poor cognitive function.
Hippocampal brain slices from CAM-α(1A)AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the α(1A)AR-selective agonist cirazoline also showed enhanced cognitive functions.
In addition, CAM-α(1A)AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-α(1A)AR mice was 10% longer than that of WT mice.
Our results suggest that long-term α(1A)AR 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.
2011-09-22
Eng.
Molecular pharmacology
Department of Pharmacology, Physiology & Therapeutics, School of Medicine & Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
Mol Pharmacol. 2011 Oct;80(4):747-58
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