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, 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.

authors

Barrot M,Olivier JD,Perrotti LI,DiLeone RJ,Berton O,Eisch AJ,Impey S,Storm DR,Neve RL,Yin JC,Zachariou V,Nestler EJ

doi

10.1073/pnas.172091899

keywords:

subject

Has Abstract

pub_date

2002-08-20 00:00:00

pages

11435-40

issue

17

eissn

0027-8424

issn

1091-6490

pii

172091899

journal_volume

99

pub_type

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