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 journalArticle

579 Citations (Scopus)

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
Externally publishedYes

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Reward
Cocaine
Dynorphins
Nucleus Accumbens
Response Elements
Opioid Receptors
Pharmaceutical Preparations
Adenosine
Carrier Proteins
Transcription Factors
Gene Expression
Brain

ASJC Scopus subject areas

  • General

Cite this

Carlezon, W. A., Thome, J., Olson, V. G., Lane-Ladd, S. B., Brodkin, E. S., Hiroi, N., ... Nestler, E. J. (1998). Regulation of cocaine reward by CREB. Science, 282(5397), 2272-2275. https://doi.org/10.1126/science.282.5397.2272

Regulation of cocaine reward by CREB. / Carlezon, William A.; Thome, Johannes; Olson, Valerie G.; Lane-Ladd, Sarah B.; Brodkin, Edward S.; Hiroi, Noboru; Duman, Ronald S.; Neve, Rachael L.; Nestler, Eric J.

In: Science, Vol. 282, No. 5397, 18.12.1998, p. 2272-2275.

Research output: Contribution to journalArticle

Carlezon, WA, Thome, J, Olson, VG, Lane-Ladd, SB, Brodkin, ES, Hiroi, N, Duman, RS, Neve, RL & Nestler, EJ 1998, 'Regulation of cocaine reward by CREB', Science, vol. 282, no. 5397, pp. 2272-2275. https://doi.org/10.1126/science.282.5397.2272
Carlezon WA, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N et al. Regulation of cocaine reward by CREB. Science. 1998 Dec 18;282(5397):2272-2275. https://doi.org/10.1126/science.282.5397.2272
Carlezon, William A. ; Thome, Johannes ; Olson, Valerie G. ; Lane-Ladd, Sarah B. ; Brodkin, Edward S. ; Hiroi, Noboru ; Duman, Ronald S. ; Neve, Rachael L. ; Nestler, Eric J. / Regulation of cocaine reward by CREB. In: Science. 1998 ; Vol. 282, No. 5397. pp. 2272-2275.
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