Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression
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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Glucocorticoid secretion patterns of transgenic mice with reduced GR resemble those patterns seen in subjects with major depression.
“glucocorticoid secretion patterns of transgenic mice with reduced GR resemble those patterns seen in subjects with major depression (Pepin et al. 1992).”
From Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis (2010) · cites this paper as Pepin et al. 1992
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“These mice, as well as those in which GR function was impaired by GR-antisense expressio”
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- Authors
- Pepin, M. C., Pothier, F., & Barden, N.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 1992-12
- Volume
- 42
- Issue
- 6
- Pages
- 991-995
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W1764422414
- Cited by
- 105
- References
- 0
- Citations by year
- 2018: 2 · 2016: 1 · 2015: 2 · 2014: 4 · 2012: 3
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- antidepressant mechanism, depression, glucocorticoid receptor, antisense RNA, transgenic mice, hypothalamic-pituitary-adrenal axis, desipramine, tricyclic antidepressants, ACTH, corticosterone, hypothalamic gene expression, dexamethasone binding
- MeSH terms
- Actins, Animals, Brain, Depression, Desipramine, Disease Models, Animal, Endocrine Glands, Hypothalamo-Hypophyseal System, Mice, Transgenic, Pituitary-Adrenal System, Receptors, Glucocorticoid, RNA, Messenger, Gene Expression, RNA, Antisense, Mice
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