cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment

J. Thome, N. Sakai, K. H. Shin, C. Steffen, Y. J. Zhang, Soren Impey, D. Storm, R. S. Duman

Research output: Contribution to journalArticle

462 Citations (Scopus)

Abstract

Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effect in vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE-LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.

Original languageEnglish (US)
Pages (from-to)4030-4036
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number11
StatePublished - Jun 1 2000
Externally publishedYes

Fingerprint

Response Elements
Antidepressive Agents
Genes
Tranylcypromine
Cyclic AMP Response Element-Binding Protein
Desipramine
Lac Operon
Monoamine Oxidase Inhibitors
Fluoxetine
Serotonin Uptake Inhibitors
Second Messenger Systems
Amygdala
Reporter Genes
Cerebral Cortex
Transgenic Mice
Hypothalamus
Hippocampus
Norepinephrine
Phosphorylation
Gene Expression

Keywords

  • β-galactosidase
  • CRE enhancer
  • Desipramine
  • Fluoxetine
  • Gene transcription
  • Phosphorylation
  • Tranylcypromine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Thome, J., Sakai, N., Shin, K. H., Steffen, C., Zhang, Y. J., Impey, S., ... Duman, R. S. (2000). cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. Journal of Neuroscience, 20(11), 4030-4036.

cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. / Thome, J.; Sakai, N.; Shin, K. H.; Steffen, C.; Zhang, Y. J.; Impey, Soren; Storm, D.; Duman, R. S.

In: Journal of Neuroscience, Vol. 20, No. 11, 01.06.2000, p. 4030-4036.

Research output: Contribution to journalArticle

Thome, J, Sakai, N, Shin, KH, Steffen, C, Zhang, YJ, Impey, S, Storm, D & Duman, RS 2000, 'cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment', Journal of Neuroscience, vol. 20, no. 11, pp. 4030-4036.
Thome, J. ; Sakai, N. ; Shin, K. H. ; Steffen, C. ; Zhang, Y. J. ; Impey, Soren ; Storm, D. ; Duman, R. S. / cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 11. pp. 4030-4036.
@article{f96844cee1f44776a8b929f7f2c18004,
title = "cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment",
abstract = "Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effect in vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE-LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.",
keywords = "β-galactosidase, CRE enhancer, Desipramine, Fluoxetine, Gene transcription, Phosphorylation, Tranylcypromine",
author = "J. Thome and N. Sakai and Shin, {K. H.} and C. Steffen and Zhang, {Y. J.} and Soren Impey and D. Storm and Duman, {R. S.}",
year = "2000",
month = "6",
day = "1",
language = "English (US)",
volume = "20",
pages = "4030--4036",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "11",

}

TY - JOUR

T1 - cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment

AU - Thome, J.

AU - Sakai, N.

AU - Shin, K. H.

AU - Steffen, C.

AU - Zhang, Y. J.

AU - Impey, Soren

AU - Storm, D.

AU - Duman, R. S.

PY - 2000/6/1

Y1 - 2000/6/1

N2 - Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effect in vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE-LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.

AB - Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effect in vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE-LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.

KW - β-galactosidase

KW - CRE enhancer

KW - Desipramine

KW - Fluoxetine

KW - Gene transcription

KW - Phosphorylation

KW - Tranylcypromine

UR - http://www.scopus.com/inward/record.url?scp=0034213455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034213455&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 4030

EP - 4036

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 11

ER -