Abstract
α2-Adrenoceptors (α2-AR) modulate many central nervous system functions, such as regulation of sympathetic tone, vigilance, attention, and reactivity to environmental stressors. Three α2-AR subtypes (α2A, α2B, and α2C) with distinct tissue-distribution patterns are known to exist, but the functional significance of each subtype is not clear. Since specific, α2-AR subtype-selective pharmacological probes are not available, mice with genetically altered α2C-AR expression were studied in order to investigate the possible involvement of the α2C-AR in physiological and behavioral responses to acute and repeated stress. A modified version of Porsolt's forced swimming test was used to assess the possible effects of altered α2C-AR expression on the development of behavioral despair. α2C-Overexpression increased and the lack of α2C-AR (α2C-KO) decreased the immobility of mice in the forced swimming test, ie α2C-AR expression appeared to promote the development of behavioral despair. In addition, α2C-KO was associated with attenuated elevation of plasma corticosterone after different stressors, and overexpression of α2C-ARs was linked with increased corticosterone levels after repeated stress. Moreover, the brain dopamine and serotonin balance, but not norepinephrine turnover, was dependent on α2C-AR expression, and the expression of c-fos and junB mRNA was increased in α2C-KO mice. Since α2C-KO produced stress-protective effects, and α2C-AR overexpression seemed to promote the development of changes related to depression, it is suggested that a yet-to-be developed subtype-selective α2C-AR antagonist might have therapeutic value in the treatment of stress-related neuropsychiatric disorders.
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Sallinen, J., Haapalinna, A., MacDonald, E. et al. Genetic alteration of the α2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels. Mol Psychiatry 4, 443–452 (1999). https://doi.org/10.1038/sj.mp.4000543
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DOI: https://doi.org/10.1038/sj.mp.4000543
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