Cited by 105Stress Responses and CortisolTreatment of Major DepressionNeuropeptides and Animal Physiology

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

Pepin, M C, Pothier, F, Barden, N·1992·Molecular Pharmacology

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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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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)
DOI: 10.1016/s0026-895x(25)09284-3
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Molecular Pharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Pharmacology (medical) › 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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Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression

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