Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues.
Proceedings of the National Academy of Sciences. 2013-02-19; 110(10): 4093-4098
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1. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4093-8. doi:
10.1073/pnas.1207531110. Epub 2013 Feb 19.
Dorsolateral caudate nucleus differentiates cocaine from natural
reward-associated contextual cues.
Liu HS(1), Chefer S, Lu H, Guillem K, Rea W, Kurup P, Yang Y, Peoples L, Stein
(1)Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural
Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Chronic drug administration induces neuroplastic changes within brain circuits
regulating cognitive control and/or emotions. Following repeated pairings between
drug intake and environmental cues, increased sensitivity to or salience of these
contextual cues provoke conscious or unconscious craving and enhance
susceptibility to relapse. To explore brain circuits participating in such
experience-induced plasticity, we combined functional MRI with a preclinical drug
vs. food self-administration (SA) withdrawal model. Specifically, two groups of
rats were trained to associate odor cues with the availability of i.v. cocaine or
oral sucrose, respectively. After 20 d of cocaine or sucrose SA followed by
prolonged (30 d) forced abstinence, animals were presented with odor cues
previously associated with or without (S+/S-) reinforcer (cocaine/sucrose)
availability while undergoing functional MRI scans. ANOVA results demonstrate
that a learning effect distinguishing S+ from S- was seen in the insula and
nucleus accumbens, with the insula response reflecting the individual history of
cocaine SA intake. A main effect of group, distinguishing cocaine from sucrose,
was seen in the medial prefrontal cortex (infralimbic, prelimbic, and cingulate
cortex) and dorsolateral striatum. Critically, only the dorsomedial striatum
demonstrated a double dissociation between the two SA groups and learning (S+ vs.
S-). These findings demonstrate altered cortico-limbic-striatal reward-related
processing to learned, environment reward-associated contextual odor cues, which
may serve as potential biomarkers for therapeutic interventions.
PMID: 23431137 [Indexed for MEDLINE]