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Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 2011 Oct; Vol. 80 (4), pp. 747-58. Date of Electronic Publication: 2011 Jul 26. - Publication Year :
- 2011
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Abstract
- 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.
- Subjects :
- Affect drug effects
Animals
Cognition drug effects
Female
Hippocampus drug effects
Hippocampus metabolism
Long-Term Potentiation drug effects
Long-Term Potentiation physiology
Longevity drug effects
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Mice, Transgenic
Neuronal Plasticity drug effects
Organ Culture Techniques
Receptors, Adrenergic, alpha-1 physiology
Synapses drug effects
Synapses physiology
Adrenergic alpha-1 Receptor Agonists pharmacology
Affect physiology
Cognition physiology
Longevity physiology
Neuronal Plasticity physiology
Receptors, Adrenergic, alpha-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0111
- Volume :
- 80
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21791575
- Full Text :
- https://doi.org/10.1124/mol.111.073734