Incubation of cocaine craving after withdrawal: a review of preclinical data.
Using a rat model of drug craving and relapse, we recently found that cocaine seeking induced by re-exposure to drug-associated cues progressively increases over the first 2 months after withdrawal from cocaine self-administration, suggesting that drug craving incubates over time [Nature 412 (2001) 141]. Here, we summarize data from studies that further characterized this incubation phenomenon and briefly discuss its implications for drug addiction. The main findings of our ongoing research are: 1. Incubation of cocaine craving is long-lasting, but not permanent: cocaine seeking induced by exposure to cocaine cues remains elevated for up to 3 months of withdrawal, but decreases after 6 months. 2. Incubation of reward craving is not drug specific: sucrose seeking induced by re-exposure to the reward cues also increases after withdrawal, but for a time period that is shorter than that of cocaine. 3. Incubation of cocaine craving is not evident after acute re-exposure to cocaine itself: cocaine seeking induced by cocaine priming injections remains essentially unchanged over the first 6 months of withdrawal. 4. Incubation of cocaine craving after withdrawal is associated with increases in the levels of brain-derived neurotrophic factor (BDNF) in mesolimbic dopamine areas.
Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Lin
L
Lu
Jeffrey W
JW
Grimm
Bruce T
BT
Hope
Yavin
Y
Shaham
D019969:Amphetamine-Related Disorders / Q000523:psychology; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D003463:Cues; D004298:Dopamine / Q000502:physiology; D005793:Generalization, Psychological; D008694:Methamphetamine; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000473:pathology / Q000523:psychology*
D019208:Brain-Derived Neurotrophic Factor; D009479:Neuropeptides; D008694:Methamphetamine; D004298:Dopamine