Regulation of cocaine reward by CREB
by
Carlezon WA Jr, Thome J, Olson VG, Lane-Ladd SB,
Brodkin ES, Hiroi N, Duman RS, Neve RL, Nestler EJ
Division of Molecular Psychiatry,
Center for Genes and Behavior,
Yale University School of Medicine and
Connecticut Mental Health Center,
New Haven, CT 06508, USA.
Science 1998 Dec 18; 282(5397):2272-5

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 kappa 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.

Pain
CREB
Tramadol
Tolerance
Nociceptin
Endomorphins
Kappa antagonism
Fentanyl and ketamine
Dynorphin and depression
Opioids, mood and cognition
Kappa upregulation and addiction

Refs
HOME
HedWeb
BLTC Research
Designer Drugs
Paradise-Engineering
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?