title: Relapse induced by cues predicting cocaine depends on rapid, transient synaptic potentiation.
abstract: Cocaine addiction is characterized by long-lasting vulnerability to relapse arising because neutral environmental stimuli become associated with drug use and then act as cues that induce relapse. It is not known how cues elicit cocaine seeking, and why cocaine seeking is more difficult to regulate than seeking a natural reward. We found that cocaine-associated cues initiate cocaine seeking by inducing a rapid, transient increase in dendritic spine size and synaptic strength in the nucleus accumbens. These changes required neural activity in the prefrontal cortex. This is not the case when identical cues were associated with obtaining sucrose, which did not elicit changes in spine size or synaptic strength. The marked cue-induced synaptic changes in the accumbens were correlated with the intensity of cocaine, but not sucrose seeking, and may explain the difficulty addicts experience in managing relapse to cocaine use.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. gipson@musc.edu
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Gipson
authors.forename: Yonatan M
authors.initials: YM
authors.lastname: Kupchik
authors.forename: Haowei
authors.initials: H
authors.lastname: Shen
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Reissner
authors.forename: Charles A
authors.initials: CA
authors.lastname: Thomas
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D004777:Environment; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D018613:Microscopy, Confocal; D009042:Motivation; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects; D012008:Recurrence; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018755:GABA Agonists; D018091:Receptors, AMPA; D018079:Receptors, GABA; D018698:Glutamic Acid; D003042:Cocaine