title: Incubation of cocaine-craving relates to glutamate over-flow within ventromedial prefrontal cortex.
abstract: Craving elicited by drug-associated cues intensifies across protracted drug abstinence - a phenomenon termed "incubation of craving" - and drug-craving in human addicts correlates with frontal cortical hyperactivity. Herein, we employed a rat model of cue-elicited cocaine-craving to test the hypothesis that the time-dependent incubation of cue-elicited cocaine-craving is associated with adaptations in dopamine and glutamate neurotransmission within the ventromedial prefrontal cortex (vmPFC). Rats were trained to self-administer intravenous cocaine (6 h/day × 10 days) and underwent in vivo microdialysis procedures during 2 h-tests for cue-elicited cocaine-craving at either 3 or 30 days withdrawal. Controls rats were trained to either self-administer sucrose pellets or received no primary reinforcer. Cocaine-seeking rats exhibited a withdrawal-dependent increase and decrease, respectively, in cue-elicited glutamate and dopamine release. These patterns of neurochemical change were not observed in either control condition. Thus, cue-hypersensitivity of vmPFC glutamate terminals is a biochemical correlate of incubated cocaine-craving that may stem from dopamine dysregulation in this region.
authors.affiliation: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.
authors.forename: Christina B
authors.initials: CB
authors.lastname: Shin
authors.affiliation: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.
authors.forename: Michela M
authors.initials: MM
authors.lastname: Serchia
authors.affiliation: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Shahin
authors.affiliation: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.
authors.forename: Micaela A
authors.initials: MA
authors.lastname: Ruppert-Majer
authors.affiliation: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.
authors.forename: Tod E
authors.initials: TE
authors.lastname: Kippin
authors.affiliation: Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA. Electronic address: karen.szumlinski@psych.ucsb.edu.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Szumlinski
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D066249:Craving / Q000187:drug effects*; D003463:Cues; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012646:Self Administration
chemical_list: D018698:Glutamic Acid; D003042:Cocaine; D004298:Dopamine
keywords: Cocaine craving; Dopamine; Glutamate; Incubation; Ventromedial prefrontal cortex