Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression.
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.
Pepin
M C
MC
Molecular Psychogenetics Laboratory, CHUL Research Centre, Ste-Foy, Québec, Canada.
Pothier
F
F
Barden
N
N
D000199:Actins / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004702:Endocrine Glands / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000235:genetics
D000199:Actins; D016372:RNA, Antisense; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003891:Desipramine