Regulation of cocaine reward by CREB

William A. Carlezon, Johannes Thome, Valerie G. Olson, Sarah B. Lane-Ladd, Edward S. Brodkin, Noboru Hiroi, Ronald S. Duman, Rachael L. Neve, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

599 Scopus citations

Abstract

Cocaine regulates the transcription factor CREB (adenosine 3',5'- monophosphate response element binding protein) in rat nucleus accumbens, a brain region that is important for addiction. Overexpression of CREB in this region decreases the rewarding effects of cocaine and makes low doses of the drug aversive. Conversely, overexpression of a dominant-negative mutant CREB increases the rewarding effects of cocaine. Altered transcription of dynorphin likely contributes to these effects: Its expression is increased by overexpression of CREB and decreased by overexpression of mutant CREB. Moreover, blockade of κ opioid receptors (on which dynorphin acts) antagonizes the negative effect of CREB on cocaine reward. These results identify an intracellular cascade - culminating in gene expression - through which exposure to cocaine modifies subsequent responsiveness to the drug.

Original languageEnglish (US)
Pages (from-to)2272-2275
Number of pages4
JournalScience
Volume282
Issue number5397
DOIs
StatePublished - Dec 18 1998

ASJC Scopus subject areas

  • General

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