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.

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