Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-10-18
pubmed:abstractText
It is well established that hypothalamic-pituitary-adrenal (HPA) axis dysregulation, characterized by elevated circulating cortisol concentrations and impaired negative feedback inhibition, is associated with affective disorders. As normalization of the HPA axis function and mood-stabilizing effects occur simultaneously during antidepressant treatment, it is likely that these effects are either directly or indirectly dependent. Although data concerning the outward transport of glucocorticoids from the brain by P-glycoprotein (Pgp) are inconsistent, it has been hypothesized that antidepressants exert their clinical activity in parts by inhibiting Pgp, subsequently leading to enhanced brain glucocorticoid levels and the normalization of the HPA axis function. Here, we report on the effects of different antidepressants (amitriptyline, fluoxetine, mirtazapine, St John's wort extract) on the brain/plasma distribution of corticosterone in mice after acute and subchronic treatment. The four antidepressants exerted different effects on the corticosterone concentration in brain and plasma. Changes in corticosterone levels were highly correlated, suggesting passive diffusion between both tissues. St John's wort extract and fluoxetine elevated brain and plasma corticosterone concentrations after subchronic treatment. Mirtazapine and amitriptyline had no effect on corticosterone concentration after subchronic treatment, possibly because both are also potent antagonists at the 5-HT2 receptor, which mediates HPA axis stimulation by serotonergic stimuli. In addition, St John's wort is the only antidepressant tested which slightly elevated Pgp protein level in the brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0893-133X
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2443-8
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Effects of antidepressants on the brain/plasma distribution of corticosterone.
pubmed:affiliation
Department of Pharmacology, Biocenter (ZAFES), University of Frankfurt, Frankfurt, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't