Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues

Hua Shan Liu, Svetlana Chefer, Hanbing Lu, Karine Guillem, William Rea, Pradeep Kurup, Yihong Yang, Laura Peoples, Elliot A. Stein

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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 experienceinduced 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 presentedwith 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 themedial prefrontal cortex (infralimbic, prelimbic, and cingulate cortex) and dorsolateral striatum. Critically, only the dorsomedial striatumdemonstrated 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.

Original languageEnglish
Pages (from-to)4093-4098
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
Publication statusPublished - Mar 5 2013
Externally publishedYes


  • Context cues
  • Drug addiction
  • Neuroplasticity

ASJC Scopus subject areas

  • General


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