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Updated: Mar 30, 2026

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Incubation of cocaine-craving relates to glutamate over-flow within ventromedial prefrontal cortex
Christina B Shin1, Michela M Serchia1, John R Shahin1
1Department of Psychological and Brain Sciences and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-9660, USA.
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.
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