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- Title
Genetic alteration of the α2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels.
- Authors
Sallinen, J.; Haapalinna, A.; MacDonald, E.; Viitamaa, T.; Lähdesmäki, J.; Rybnikova, E.; Pelto-Huikko, M.; Kobilka, B.K.; Scheinin, M.
- Abstract
α[sub 2]-Adrenoceptors (α[sub 2]-AR) modulate many central nervous system functions, such as regulation of sympathetic tone, vigilance, attention, and reactivity to environmental stressors. Three α[sub 2]-AR subtypes (α[sub 2A], α[sub 2B], and α[sub 2C]) with distinct tissue-distribution patterns are known to exist, but the functional significance of each subtype is not clear. Since specific, α[sub 2]-AR subtype-selective pharmacological probes are not available, mice with genetically altered α[sub 2C]AR expression were studied in order to investigate the possible involvement of the α[sub 2C]-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 α[sub 2C]-AR expression on the development of behavioral despair. α[sub 2C]-Overexpression increased and the lack of α[sub 2C]-AR (α[sub 2C]-KO) decreased the immobility of mice in the forced swimming test, ie α[sub 2C]AR expression appeared to promote the development of behavioral despair. In addition, α[sub 2C]KO was associated with attenuated elevation of plasma corticosterone after different stressors, and overexpression of α[sub 2C]-ARs was linked with increased corticosterone levels after repeated stress. Moreover, the brain dopamine and serotonin balance, but not norepinephrine turnover, was dependent on α[sub 2C]-AR expression, and the expression of c-fos and junB mRNA was increased in α[sub 2C]-KO mice. Since α[sub 2C]-KO produced stress-protective effects, and α[sub 2C]-AR overexpression seemed to promote the development of changes related to depression, it is suggested that a yet-to-be developed subtype-selective α[sub 2C]-AR antagonist might have therapeutic value in the treatment of stress-related neuropsychiatric disorders.
- Subjects
ADRENERGIC receptors; CENTRAL nervous system; LABORATORY mice
- Publication
Molecular Psychiatry, 1999, Vol 4, Issue 5, p443
- ISSN
1359-4184
- Publication type
Article
- DOI
10.1038/sj.mp.4000543