Genetic alteration of the alpha(2)-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels

Citation
J. Sallinen et al., Genetic alteration of the alpha(2)-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels, MOL PSYCHI, 4(5), 1999, pp. 443-452
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR PSYCHIATRY
ISSN journal
1359-4184 → ACNP
Volume
4
Issue
5
Year of publication
1999
Pages
443 - 452
Database
ISI
SICI code
1359-4184(199909)4:5<443:GAOTAS>2.0.ZU;2-7
Abstract
alpha(2)-Adrenoceptors (alpha(2)-AR) modulate many central nervous system f unctions, such as regulation of sympathetic tone, vigilance, attention, and reactivity to environmental stressors. Three alpha(2)-AR subtypes (alpha(2 A), alpha(2B), and alpha(2C)) with distinct tissue-distribution patterns ar e known to exist, but the functional significance of each subtype is; not c lear. Since specific, alpha(2)-AR subtype-selective pharmacological probes are! not available, mice with genetically altered alpha(2C)-AR expression w ere studied in order to investigate the possible involvement of the alpha(2 C)-AR in physiological and behavioral responses to acute and repeated stres s. A modified version of Porsolt's forced swimming test was used to assess the possible effects of altered alpha(2C)-AR expression on the development of behavioral despair. alpha(2C)-Overexpression increased and the lack of a lpha(2C)-AR (alpha(2C)-KO) decreased the immobility of mice in the forced s wimming test, ie alpha(2C)-AR expression appeared to promote the developmen t of behavioral despair. In addition, alpha(2C)-KO was associated with atte nuated elevation of plasma corticosterone after different stressors, and ov erexpression of alpha(2C)-ARs was linked with increased corticosterone leve ls after repeated stress, Moreover, the brain dopamine and serotonin balanc e, but not norepinephrine turnover, was dependent on alpha(2C)-AR expressio n, and the expression of c-fos and junB mRNA was increased in alpha(2C)-KO mice. Since alpha(2C)-KO produced stress-protective effects, and alpha(2C)- AR overexpression seemed to promote the development of changes related to d epression, it is suggested that a yet-to-be developed subtype-selective alp ha(2C)-AR antagonist might have therapeutic value in the treatment of stres s-related neuropsychiatric disorders.