Cocaine and CREB

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Science  18 Dec 1998:
Vol. 282, Issue 5397, pp. 2149
DOI: 10.1126/science.282.5397.2149n

Psychoactive drug use can cause permanent molecular adaptations of neurons in the brain. Carlezon et al. (p. 2272) investigated a sequence of events in cells of the nucleus accumbens after exposure to cocaine. Chronic cocaine is known to increase adenosine 3′,5′-monophosphate (cAMP) formation and subsequently increase activity of cAMP-dependent protein kinase A (PKA). These events in turn increase phosphorylation of the transcription factor CREB (cAMP responsive binding element protein). The authors used virus-induced transient overexpression of normal CREB and a defective mutant to show that CREB effects the expression of dynorphin. Dynorphin is a well-known endogenous ligand for κ-opioid receptors that are involved in the valence (reward versus aversion) of cocaine action.

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