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  • Title: Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression.
    Author: Pepin MC, Pothier F, Barden N.
    Journal: Mol Pharmacol; 1992 Dec; 42(6):991-5. PubMed ID: 1480137.
    Abstract:
    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.
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