Cue-Induced Cocaine Seeking and Relapse Are Reduced by Disruption of Drug Memory Reconsolidation

Lee, Jonathan; Milton, Amy; Everitt, Barry J.

doi:10.1523/jneurosci.0323-06.2006

Cited by 270 publications

(278 citation statements)

References 38 publications

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“…More recently though, decreases in EGR1 mRNA expression have been documented during forced abstinence from highdose cocaine self-administration binges (Mutschler et al, 2000). The potential importance of EGR1 in cocaine-related behaviors has been demonstrated in antisense injection and mutant mouse experiments (Lee et al, 2005(Lee et al, , 2006Valjent et al, 2006). The finding of decreases in histone H3 acetylation at 1 and 10 days of abstinence suggests a decrease in active transcription of EGR1.…”

Section: Discussionmentioning

confidence: 99%

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Freeman

Patel

Brucklacher

et al. 2007

Neuropsychopharmacol

110

126

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Cocaine-responsive gene expression changes have been described after either no drug abstinence or short periods of abstinence. Little data exist on the persistence of these changes after long-term abstinence. Previously, we reported that after discrete-trial cocaine selfadministration and 10 days of forced abstinence, incubation of cocaine reinforcement was observable by a progressive ratio schedule. The present study used rat discrete-trial cocaine self-administration and long-term forced abstinence to examine extinction responding, mRNA abundance of known cocaine-responsive genes, and chromatin remodeling. At 30 and 100 days of abstinence, extinction responding increased compared to 3-day abstinent rats. Decreases in both medial prefrontal cortex (mPFC) and nucleus accumbens cfos, Nr4a1, Arc, and EGR1 mRNA were observed, and in most cases persisted, for 100 days of abstinence. The signaling peptides CART and neuropeptide Y (NPY) transiently increased in the mPFC, but returned to baseline levels following 10 days of abstinence. To investigate a potential regulatory mechanism for these persistent mRNA changes, levels of histone H3 acetylation at promoters for genes with altered mRNA expression were examined. In the mPFC, histone H3 acetylation decreased after 1 and 10 days of abstinence at the promoter for EGR1. H3 acetylation increased for NPY after 1 day of abstinence and returned to control levels by 10 days of abstinence.Behaviorally, these results demonstrate incubation after discrete-trial cocaine self-administration and prolonged forced abstinence. This incubation is accompanied by changes in gene expression that persist long after cessation of drug administration and may be regulated by chromatin remodeling.

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Section: Discussionmentioning

confidence: 99%

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Freeman

Patel

Brucklacher

et al. 2007

Neuropsychopharmacol

110

126

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“…However, as in prior studies of UPS activation after fear conditioning (Jarome et al, 2011), our dissection did not differentiate subregions of the amygdala. Although the basolateral amygdala has a key role in cocaine memory reconsolidation (eg, Lee et al, 2006), it is the central nucleus that is strongly implicated in the incubation of cocaine craving (Lu et al, 2005a(Lu et al, ,b, 2007; also see Lee et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to well-established roles for NMDA receptors and downstream signaling pathways (Torregrossa and Taylor, 2013), de novo protein synthesis is necessary for retrieval and/or reconsolidation of cocaine memories (Lee et al, 2006;Fuchs et al, 2009;Fan et al, 2010;Théberge et al, 2010;Bailey et al, 2012;Ren et al, 2013;Shi et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration

Werner

Milovanovic

Christian

et al. 2015

Neuropsychopharmacol

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The ubiquitin-proteasome system (UPS) has been implicated in the retrieval-induced destabilization of cocaine-and fear-related memories in Pavlovian paradigms. However, nothing is known about its role in memory retrieval after self-administration of cocaine, an operant paradigm, or how the length of withdrawal from cocaine may influence retrieval mechanisms. Here, we examined UPS activity after an extended-access cocaine self-administration regimen that leads to withdrawal-dependent incubation of cue-induced cocaine craving. Controls self-administered saline. In initial experiments, memory retrieval was elicited via a cue-induced seeking/retrieval test on withdrawal day (WD) 50-60, when craving has incubated. We found that retrieval of cocaine-and saline-associated memories produced similar increases in polyubiquitinated proteins in the nucleus accumbens (NAc), compared with rats that did not undergo a seeking/retrieval test. Measures of proteasome catalytic activity confirmed similar activation of the UPS after retrieval of saline and cocaine memories. However, in a subsequent experiment in which testing was conducted on WD1, proteasome activity in the NAc was greater after retrieval of cocaine memory than saline memory. Analysis of other brain regions confirmed that effects of cocaine memory retrieval on proteasome activity, relative to saline memory retrieval, depend on withdrawal time. These results, combined with prior studies, suggest that the relationship between UPS activity and memory retrieval depends on training paradigm, brain region, and time elapsed between training and retrieval. The observation that mechanisms underlying cocaine memory retrieval change depending on the age of the memory has implications for development of memory destabilization therapies for cue-induced relapse in cocaine addicts.

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“…Studies from our laboratory have shown that appetitive drug memories undergo protein synthesis-dependent reconsolidation in the BLA. Intra-BLA infusions of antisense oligodeoxynucleotides (ASOs) targeting the immediate-early gene Zif268 before memory reactivation of a CS-cocaine or CS-fear association resulted in a significant reactivation-dependent reconsolidation deficit (Lee et al, 2005) and prevented cue-maintained cocaine seeking and cue-induced relapse (Lee et al, 2006). Expression of Zif268 is upregulated in the BLA after reexposure to CSs previously paired with both cocaine (Thomas et al, 2003) and footshock (Hall et al, 2001), and intra-BLA Zif268 ASO knocks down Zif268 protein in the BLA after reexposure to a CS paired with footshock (Lee et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Disrupting Reconsolidation of Conditioned Withdrawal Memories in the Basolateral Amygdala Reduces Suppression of Heroin Seeking in Rats

Hellemans¹,

Everitt²

2006

J. Neurosci.

Self Cite

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Recent data from our laboratory have demonstrated that appetitive drug memories undergo protein synthesis-dependent reconsolidation in the basolateral amygdala (BLA), an area important in the formation of emotional memories. We here investigated the importance of the BLA in the reconsolidation of opiate conditioned withdrawal memories. Rats with bilateral cannulas implanted in the BLA were trained to respond for heroin (0.12 mg/kg, i.v.) under a seeking-taking schedule, which required responding on a seeking lever to gain the opportunity to self-administer heroin by a single response on a taking lever. After induction of opiate dependence with subcutaneously implanted, heroin-filled osmotic minipumps (3 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 heroin), rats received five consecutive pairings of a conditioned stimulus (CS) (tone, light, and odor compound) paired with naloxone (0.10 mg/kg, s.c.)-precipitated withdrawal. We replicated our previous findings that heroin seeking is suppressed in the presence of the withdrawal-associated CS. However, infusion of Zif268 antisense oligodeoxynucleotide into the BLA before reactivation of the CS-withdrawal association abolished this conditioned suppression in a reactivation-dependent manner. We also report that reconsolidation of CS-withdrawal memories upregulates Zif268 protein in the basolateral but not central nucleus of the amygdala and that Zif268 knockdown occurs selectively in the BLA. These results demonstrate that drug withdrawal memories undergo protein synthesis-dependent reconsolidation in the BLA and suggest a common mechanism for the reconsolidation of both appetitive and aversive drug memories.

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Cue-Induced Cocaine Seeking and Relapse Are Reduced by Disruption of Drug Memory Reconsolidation

Cited by 270 publications

References 38 publications

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Persistent Alterations in Mesolimbic Gene Expression with Abstinence from Cocaine Self-Administration

Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration

Disrupting Reconsolidation of Conditioned Withdrawal Memories in the Basolateral Amygdala Reduces Suppression of Heroin Seeking in Rats

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