Renewal of extinguished cocaine-seeking

School of Psychology, The University of New South Wales, Sydney, New South Wales, 2052, Australia.
Neuroscience (Impact Factor: 3.36). 03/2008; 151(3):659-70. DOI: 10.1016/j.neuroscience.2007.11.018
Source: PubMed


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.

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Available from: Adam S Hamlin
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    • "Immunohistochemical assays indicated that Fos expression is increased during cocaine or heroin self-administration throughout the corticostriatal circuitry, including medial prefrontal and orbitofrontal cortex, nucleus accumbens core and shell subregions, and the dorsal striatum (Ben-Shahar et al., 2004; Larson et al., 2010; Madsen et al., 2012; Martin- Garcia et al., 2014; Pich et al., 1997; Thiel et al., 2010; Zahm et al., 2010). Even when drug is not onboard, contextual cues and discrete cues previously paired with drug selfadministration activate many of the same prefrontal cortex and striatal areas during reinstatement of lever pressing (Bastle et al., 2012; Bossert et al., 2011; Cruz et al., 2014; Fanous et al., 2012; Fanous et al., 2013; Hamlin et al., 2008; Kufahl et al., 2009; Mahler and Aston-Jones, 2012; Neisewander et al., 2000; Shalev et al., 2003; Zavala et al., 2007; Zhou et al., 2013) or exposure to the paired context alone without lever responding (Doherty et al., 2013). Perhaps due to higher variability, in situ hybridization and quantitative PCR assays for c-fos mRNA identify activation of only a subset of these same brain areas (Celentano et al., 2009; Daunais et al., 1993; Daunais et al., 1995; Hearing et al., 2008a; Hearing et al., 2008b; Koya et al., 2006; Kuntz et al., 2008; Kuzmin and Johansson, 1999). "
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    • "Finally, brain regions that were robustly activated during inhibition of cocaine seeking were also previously shown to be involved in triggering cocaine seeking. This was the case for the PL, NAc core, LH, and VTA (McFarland et al. 2003, 2004; Harris et al. 2005; Hamlin et al. 2008; Marchant et al. 2009). Regarding the PL, this apparent contradiction may be resolved by postulating that the PL has a more general function in controlling cocaine seeking than inhibition or excitation per se. "
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    • "Until recently, the degree to which it did had been unclear. Although ABA renewal had been routinely demonstrated with either food or drug reinforcers (e.g., Bossert et al., 2004; Chaudri et al., 2009; Crombag and Shaham, 2002; Hamlin et al., 2007, 2008; Nakajima et al., 2000; Welker and McAuley, 1978; Zironi et al., 2006), several reports had failed to demonstrate AAB renewal (see Bossert et al., 2004; Crombag and Shaham, 2002; Nakajima et al., 2000) and the evidence for ABC renewal was mixed (e.g., Zironi et al., 2006). The lack of evidence of AAB and ABC renewal left unanswered the crucial question of whether mere removal from the extinction context was sufficient to cause response recovery. "
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