CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli

Michel Barrot, Jocelien D A Olivier, Linda I. Perrotti, Ralph J. DiLeone, Olivier Berton, Amelia J. Eisch, Soren Impey, Daniel R. Storm, Rachael L. Neve, Jerry C. Yin, Venetia Zachariou, Eric J. Nestler

Research output: Contribution to journalArticle

367 Citations (Scopus)

Abstract

The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggesting an active role of CREB in adaptive processes that follow exposure to drugs of abuse. Using CRE-LacZ reporter mice, we show that not only rewarding stimuli such as morphine, but also aversive stimuli such as stress, activate CRE-mediated transcription in the nucleus accumbens shell. Using viral-mediated gene transfer to locally alter the activity of CREB, we show that this manipulation affects morphine reward, I as well as the preference for sucrose, a more natural reward. We then show that local changes in CREB activity induce a more general syndrome, by altering reactions to anxiogenic, aversive, and nociceptive stimuli as well. Increased CREB activity in the nucleus accumbens shell decreases an animal's responses to each of these stimuli, whereas decreased CREB activity induces an opposite phenotype. These results show that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses. This control appears to be independent of the intrinsic appetitive or aversive value of the stimulus. The potential relevance of these data to addiction and mood disorders is discussed.

Original languageEnglish (US)
Pages (from-to)11435-11440
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number17
DOIs
StatePublished - Aug 20 2002

Fingerprint

Nucleus Accumbens
Carrier Proteins
Reward
Response Elements
Street Drugs
Morphine
Animal Shells
Cyclic AMP Response Element-Binding Protein
Neuronal Plasticity
Viral Genes
Brain
Mood Disorders
Cocaine
Sucrose
Transcription Factors
Phenotype

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. / Barrot, Michel; Olivier, Jocelien D A; Perrotti, Linda I.; DiLeone, Ralph J.; Berton, Olivier; Eisch, Amelia J.; Impey, Soren; Storm, Daniel R.; Neve, Rachael L.; Yin, Jerry C.; Zachariou, Venetia; Nestler, Eric J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 17, 20.08.2002, p. 11435-11440.

Research output: Contribution to journalArticle

Barrot, M, Olivier, JDA, Perrotti, LI, DiLeone, RJ, Berton, O, Eisch, AJ, Impey, S, Storm, DR, Neve, RL, Yin, JC, Zachariou, V & Nestler, EJ 2002, 'CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli', Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 17, pp. 11435-11440. https://doi.org/10.1073/pnas.172091899
Barrot, Michel ; Olivier, Jocelien D A ; Perrotti, Linda I. ; DiLeone, Ralph J. ; Berton, Olivier ; Eisch, Amelia J. ; Impey, Soren ; Storm, Daniel R. ; Neve, Rachael L. ; Yin, Jerry C. ; Zachariou, Venetia ; Nestler, Eric J. / CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 17. pp. 11435-11440.
@article{31f0cf7c74ee428295b7804bea579cd7,
title = "CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli",
abstract = "The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggesting an active role of CREB in adaptive processes that follow exposure to drugs of abuse. Using CRE-LacZ reporter mice, we show that not only rewarding stimuli such as morphine, but also aversive stimuli such as stress, activate CRE-mediated transcription in the nucleus accumbens shell. Using viral-mediated gene transfer to locally alter the activity of CREB, we show that this manipulation affects morphine reward, I as well as the preference for sucrose, a more natural reward. We then show that local changes in CREB activity induce a more general syndrome, by altering reactions to anxiogenic, aversive, and nociceptive stimuli as well. Increased CREB activity in the nucleus accumbens shell decreases an animal's responses to each of these stimuli, whereas decreased CREB activity induces an opposite phenotype. These results show that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses. This control appears to be independent of the intrinsic appetitive or aversive value of the stimulus. The potential relevance of these data to addiction and mood disorders is discussed.",
author = "Michel Barrot and Olivier, {Jocelien D A} and Perrotti, {Linda I.} and DiLeone, {Ralph J.} and Olivier Berton and Eisch, {Amelia J.} and Soren Impey and Storm, {Daniel R.} and Neve, {Rachael L.} and Yin, {Jerry C.} and Venetia Zachariou and Nestler, {Eric J.}",
year = "2002",
month = "8",
day = "20",
doi = "10.1073/pnas.172091899",
language = "English (US)",
volume = "99",
pages = "11435--11440",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "17",

}

TY - JOUR

T1 - CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli

AU - Barrot, Michel

AU - Olivier, Jocelien D A

AU - Perrotti, Linda I.

AU - DiLeone, Ralph J.

AU - Berton, Olivier

AU - Eisch, Amelia J.

AU - Impey, Soren

AU - Storm, Daniel R.

AU - Neve, Rachael L.

AU - Yin, Jerry C.

AU - Zachariou, Venetia

AU - Nestler, Eric J.

PY - 2002/8/20

Y1 - 2002/8/20

N2 - The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggesting an active role of CREB in adaptive processes that follow exposure to drugs of abuse. Using CRE-LacZ reporter mice, we show that not only rewarding stimuli such as morphine, but also aversive stimuli such as stress, activate CRE-mediated transcription in the nucleus accumbens shell. Using viral-mediated gene transfer to locally alter the activity of CREB, we show that this manipulation affects morphine reward, I as well as the preference for sucrose, a more natural reward. We then show that local changes in CREB activity induce a more general syndrome, by altering reactions to anxiogenic, aversive, and nociceptive stimuli as well. Increased CREB activity in the nucleus accumbens shell decreases an animal's responses to each of these stimuli, whereas decreased CREB activity induces an opposite phenotype. These results show that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses. This control appears to be independent of the intrinsic appetitive or aversive value of the stimulus. The potential relevance of these data to addiction and mood disorders is discussed.

AB - The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggesting an active role of CREB in adaptive processes that follow exposure to drugs of abuse. Using CRE-LacZ reporter mice, we show that not only rewarding stimuli such as morphine, but also aversive stimuli such as stress, activate CRE-mediated transcription in the nucleus accumbens shell. Using viral-mediated gene transfer to locally alter the activity of CREB, we show that this manipulation affects morphine reward, I as well as the preference for sucrose, a more natural reward. We then show that local changes in CREB activity induce a more general syndrome, by altering reactions to anxiogenic, aversive, and nociceptive stimuli as well. Increased CREB activity in the nucleus accumbens shell decreases an animal's responses to each of these stimuli, whereas decreased CREB activity induces an opposite phenotype. These results show that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses. This control appears to be independent of the intrinsic appetitive or aversive value of the stimulus. The potential relevance of these data to addiction and mood disorders is discussed.

UR - http://www.scopus.com/inward/record.url?scp=0037143736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037143736&partnerID=8YFLogxK

U2 - 10.1073/pnas.172091899

DO - 10.1073/pnas.172091899

M3 - Article

C2 - 12165570

AN - SCOPUS:0037143736

VL - 99

SP - 11435

EP - 11440

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -