Renewal of extinguished cocaine-seeking

A. S. Hamlin, K. J. Clemens, G. P. McNally*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    123 Citations (Scopus)

    Abstract

    Rats were trained to self-administer cocaine in a distinctive context (context A). They were then extinguished in a second context (context B) prior to test for cocaine-seeking in the original training context, context A (group ABA), context B (group ABB) or no test (group AB0). Group ABA showed renewal of extinguished cocaine-seeking associated with c-Fos induction in basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Groups ABA and ABB showed test-associated c-Fos induction in prelimbic prefrontal cortex, nucleus accumbens (core, shell, rostral pole), striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area. Double immunofluorescence revealed that renewal-associated c-Fos was expressed in orexin-negative lateral hypothalamic neurons whereas test-associated c-Fos was expressed in orexin-positive perifornical hypothalamic neurons. Retrograde tracing from lateral hypothalamus with cholera toxin revealed only sparse dual-labeled neurons in basolateral amygdala and infralimbic prefrontal cortex, suggesting that these regions contribute to renewal of cocaine-seeking independently of their projections to lateral hypothalamus. Retrograde tracing from the ventral tegmental area suggested that hypothalamic contributions to cocaine-seeking are likewise independent of projections to the midbrain. These results suggest that renewal of cocaine-seeking depends critically on basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Whereas basolateral amygdala and lateral hypothalamus contributions may be common to renewal of extinguished cocaine-, alcohol-, and sucrose-seeking, infralimbic prefrontal cortex contributions appear unique to renewal of cocaine-seeking and may reflect the habitual nature of relapse to cocaine.

    Original languageEnglish
    Pages (from-to)659-670
    Number of pages12
    JournalNeuroscience
    Volume151
    Issue number3
    DOIs
    Publication statusPublished - 6 Feb 2008

    Keywords

    • cocaine
    • orexin
    • rat
    • reinstatement
    • relapse
    • tracing

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