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

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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
Issue number5397
StatePublished - Dec 18 1998

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    Carlezon, W. A., Thome, J., Olson, V. G., Lane-Ladd, S. B., Brodkin, E. S., Hiroi, N., Duman, R. S., Neve, R. L., & Nestler, E. J. (1998). Regulation of cocaine reward by CREB. Science, 282(5397), 2272-2275.