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.
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U2 - 10.1073/pnas.172091899
DO - 10.1073/pnas.172091899
M3 - Article
C2 - 12165570
AN - SCOPUS:0037143736
SN - 0027-8424
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
IS - 17
ER -