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Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression

MC Pepin, F Pothier and N Barden

Molecular Psychogenetics Laboratory, CHUL Research Centre, Ste-Foy, Quebec, Canada.

We have created transgenic mouse lines with impaired glucocorticoid receptor function by expression of a type II glucocorticoid receptor antisense RNA in brain tissues. These animals have endocrinological characteristics similar to those seen in depression, including a hyperactive hypothalamic-pituitary-adrenal axis as indicated by elevated plasma corticosterone and adrenocorticotropin hormone levels. Treatment of transgenic animals with the tricyclic antidepressant desipramine increased hypothalamic glucocorticoid receptor mRNA concentration and dexamethasone-binding activity while decreasing plasma adrenocorticotropin hormone concentration and corticosterone levels. These results support the hypothesis that antidepressants exert action on the hypothalamic-pituitary-adrenal axis through modulation of glucocorticoid receptor gene expression.

Volume 42, Issue 6, pp. 991-995, 12/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics