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 language | English (US) |
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Pages (from-to) | 2272-2275 |
Number of pages | 4 |
Journal | Science |
Volume | 282 |
Issue number | 5397 |
DOIs | |
State | Published - Dec 18 1998 |
Externally published | Yes |
ASJC Scopus subject areas
- General