Central amygdala ERK signaling pathway is critical to incubation of cocaine craving.
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.
Lu
Lin
L
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.
Hope
Bruce T
BT
Dempsey
Jack
J
Liu
Shirley Y
SY
Bossert
Jennifer M
JM
Shaham
Yavin
Y
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000779:Anesthetics, Local; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D002070:Butadienes / Q000494:pharmacology; D003042:Cocaine / Q000633:toxicity; D019970:Cocaine-Related Disorders / Q000150:complications / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005502:Food; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D012646:Self Administration; D015398:Signal Transduction / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors
D000779:Anesthetics, Local; D002070:Butadienes; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D009570:Nitriles; C113580:U 0126; D016202:N-Methylaspartate; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine