Central amygdala ERK signaling pathway is critical
to incubation of cocaine craving

by
Lu L, Hope BT, Dempsey J, Liu SY, Bossert JM, Shaham Y.
Behavioral Neuroscience Branch,
Intramural Research Program/
National Institute on Drug Abuse,
National Institutes of Health,
Department of Health and Human Services,
5500 Nathan Shock Drive,
Baltimore, Maryland 21224, USA.
Nat Neurosci. 2005 Jan 16


ABSTRACT

Using a rat model of craving and relapse, we have previously found time-dependent increases in cue-induced cocaine seeking over the first months of withdrawal from cocaine, suggesting that drug craving incubates over time. Here, we explored the role of the amygdala extracellular signal-regulated kinase (ERK) signaling pathway in this incubation. Cocaine seeking induced by exposure to cocaine cues was substantially higher after 30 withdrawal days than after 1 withdrawal day. Exposure to these cues increased ERK phosphorylation in the central, but not the basolateral, amygdala after 30 d, but not 1 d, of withdrawal. After 30 d of withdrawal from cocaine, inhibition of central, but not basolateral, amygdala ERK phosphorylation decreased cocaine seeking. After 1 d of withdrawal, stimulation of central amygdala ERK phosphorylation increased cocaine seeking. Results suggest that the incubation of cocaine craving is mediated by time-dependent increases in the responsiveness of the central amygdala ERK pathway to cocaine cues.


The amygdala
Cocaine hotspots
The coke-craving brain
Freebasing flies go hyperkinetic
Cocaine, alcohol and cocaethylene
Cocaethylene and cocaine dependence

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