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

Lin Lu; Bruce T Hope; Jack Dempsey; Shirley Y Liu; Jennifer M Bossert; Yavin Shaham

doi:10.1038/nn1383

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

Nat Neurosci. 2005 Feb;8(2):212-9. doi: 10.1038/nn1383. Epub 2005 Jan 16.

Authors

Lin Lu¹, Bruce T Hope, Jack Dempsey, Shirley Y Liu, Jennifer M Bossert, Yavin Shaham

Affiliation

¹ 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.

PMID: 15657599
DOI: 10.1038/nn1383

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.

Publication types

Comparative Study
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amygdala / drug effects
Amygdala / metabolism*
Anesthetics, Local
Animals
Behavior, Addictive / metabolism
Behavior, Animal
Blotting, Western / methods
Butadienes / pharmacology
Cocaine / toxicity
Cocaine-Related Disorders / complications
Cocaine-Related Disorders / metabolism*
Conditioning, Operant / drug effects
Cues
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology
Excitatory Amino Acid Agonists / pharmacology
Extinction, Psychological / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism*
Food
Injections, Intravenous / methods
Male
N-Methylaspartate / pharmacology
Nitriles / pharmacology
Phosphorylation / drug effects
Rats
Rats, Long-Evans
Reinforcement, Psychology
Self Administration
Signal Transduction / physiology*
Substance Withdrawal Syndrome / etiology
Time Factors

Substances

Anesthetics, Local
Butadienes
Enzyme Inhibitors
Excitatory Amino Acid Agonists
Nitriles
U 0126
N-Methylaspartate
Extracellular Signal-Regulated MAP Kinases
Cocaine