Inducible and brain region-specific CREB transgenic mice

Norio Sakai, Johannes Thome, Samuel S. Newton, Jingshan Chen, Max B. Kelz, Cathy Steffen, Eric J. Nestler, Ronald S. Duman

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.

Original languageEnglish (US)
Pages (from-to)1453-1464
Number of pages12
JournalMolecular pharmacology
Volume61
Issue number6
DOIs
StatePublished - Jun 10 2002

Fingerprint

Cyclic AMP Response Element-Binding Protein
Transgenic Mice
Brain
Tetracycline
Street Drugs
Activating Transcription Factors
Dynorphins
Trans-Activators
Phosphopyruvate Hydratase
Doxycycline
Psychotropic Drugs
Gyrus Cinguli
Nucleus Accumbens
Locomotion
Neuropeptides
Cocaine
Gene Expression

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Sakai, N., Thome, J., Newton, S. S., Chen, J., Kelz, M. B., Steffen, C., ... Duman, R. S. (2002). Inducible and brain region-specific CREB transgenic mice. Molecular pharmacology, 61(6), 1453-1464. https://doi.org/10.1124/mol.61.6.1453

Inducible and brain region-specific CREB transgenic mice. / Sakai, Norio; Thome, Johannes; Newton, Samuel S.; Chen, Jingshan; Kelz, Max B.; Steffen, Cathy; Nestler, Eric J.; Duman, Ronald S.

In: Molecular pharmacology, Vol. 61, No. 6, 10.06.2002, p. 1453-1464.

Research output: Contribution to journalArticle

Sakai, N, Thome, J, Newton, SS, Chen, J, Kelz, MB, Steffen, C, Nestler, EJ & Duman, RS 2002, 'Inducible and brain region-specific CREB transgenic mice', Molecular pharmacology, vol. 61, no. 6, pp. 1453-1464. https://doi.org/10.1124/mol.61.6.1453
Sakai N, Thome J, Newton SS, Chen J, Kelz MB, Steffen C et al. Inducible and brain region-specific CREB transgenic mice. Molecular pharmacology. 2002 Jun 10;61(6):1453-1464. https://doi.org/10.1124/mol.61.6.1453
Sakai, Norio ; Thome, Johannes ; Newton, Samuel S. ; Chen, Jingshan ; Kelz, Max B. ; Steffen, Cathy ; Nestler, Eric J. ; Duman, Ronald S. / Inducible and brain region-specific CREB transgenic mice. In: Molecular pharmacology. 2002 ; Vol. 61, No. 6. pp. 1453-1464.
@article{f8695ec08fe9485f875102af466871e5,
title = "Inducible and brain region-specific CREB transgenic mice",
abstract = "To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.",
author = "Norio Sakai and Johannes Thome and Newton, {Samuel S.} and Jingshan Chen and Kelz, {Max B.} and Cathy Steffen and Nestler, {Eric J.} and Duman, {Ronald S.}",
year = "2002",
month = "6",
day = "10",
doi = "10.1124/mol.61.6.1453",
language = "English (US)",
volume = "61",
pages = "1453--1464",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "6",

}

TY - JOUR

T1 - Inducible and brain region-specific CREB transgenic mice

AU - Sakai, Norio

AU - Thome, Johannes

AU - Newton, Samuel S.

AU - Chen, Jingshan

AU - Kelz, Max B.

AU - Steffen, Cathy

AU - Nestler, Eric J.

AU - Duman, Ronald S.

PY - 2002/6/10

Y1 - 2002/6/10

N2 - To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.

AB - To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different lines of bitransgenic mice, and CREB expression was blocked by addition of doxycycline, an analog of tetracycline. Overexpression of CREB influenced the expression of other members of the CREB/ATF family of transcription factors, consistent with previous reports. In addition, psychostimulant induction of dynorphin, a neuropeptide regulated by drugs of abuse, was up-regulated in striatum. Finally, there was a significant reduction in cocaine-induced locomotor activity in the CREB bitransgenic mice. These results are consistent with a role for CREB in mediating adaptive changes that occur in response to drugs of abuse.

UR - http://www.scopus.com/inward/record.url?scp=0036262777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036262777&partnerID=8YFLogxK

U2 - 10.1124/mol.61.6.1453

DO - 10.1124/mol.61.6.1453

M3 - Article

C2 - 12021407

AN - SCOPUS:0036262777

VL - 61

SP - 1453

EP - 1464

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 6

ER -