Journal
NEUROPHARMACOLOGY
Volume 102, Issue -, Pages 103-110Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.10.038
Keywords
Incubation; Cocaine craving; Ventromedial prefrontal cortex; Glutamate; Dopamine
Categories
Funding
- NIH [DA024038]
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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 x 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. (c) 2015 Elsevier Ltd. All rights reserved.
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