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Long‐Term Antidepressant Treatment Reduces Behavioural Deficits in Transgenic Mice with Impaired Glucocorticoid Receptor Function
Author(s) -
Montkowski Alexandra,
Barden Nicholas,
Wotjak Carsten,
Stec Ingemar,
Ganster Julia,
Meaney Michael,
Engelmann Mario,
Reul Johannes M. H. M.,
Landgraf Rainer,
Holsboer Florian
Publication year - 1995
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1995.tb00724.x
Subject(s) - antidepressant , moclobemide , endocrinology , medicine , glucocorticoid , behavioural despair test , glucocorticoid receptor , genetically modified mouse , monoamine neurotransmitter , transgene , psychology , receptor , serotonin , biology , hippocampus , biochemistry , gene
Impaired cognitive function and enhanced activity of the hypothalamic‐pituitary‐adrenocortical system are among the cardinal symptoms of major depression in humans that resolve after successful antidepressant treatment. We used a transgenic mouse model expressing antisense RNA complementary to that of glucocorticoid receptor (GR) mRNA to test the hypothesis that reduced GR function can cause these clinical disturbances. The transgenic mice show profound behavioural changes in a number of animal tests that are indicative of cognitive impairment. These mice also have elevated plasma corticotropin concentrations in response to stress. After long‐term treatment with moclobemide, a reversible inhibitor of monoamine oxidase type A that acts clinically as an antidepressant, both the behavioural deficits and the hormonal alterations disappeared. These observations suggest that a transgenic mouse with GR dysfunction may be a useful model for investigation of drug effects on the cognitive and neuroendocrine aspects of depression.