Li F, Xue Y, Wang J, Fang Q, Li Y, Zhu W et al. Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of memories for cocaine cues. J Neurosci 30: 10351-10359

School of Pharmacy and Affiliated Hospital of Guiyang Medical University, Guiyang 550004, China.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2010; 30(31):10351-9. DOI: 10.1523/JNEUROSCI.2112-10.2010
Source: PubMed


Cocaine use and relapse involves learned associations between cocaine-associated environmental contexts and discrete stimuli and cocaine effects. Initially, these contextual and discrete cues undergo memory consolidation after being paired with cocaine exposure. During abstinence, cocaine cue memories can undergo memory reconsolidation after cue exposure without the drug. We used a conditioned place preference (CPP) procedure in rats to study the role of neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) in consolidation and reconsolidation of cocaine cue memories. We found that the expression of cocaine CPP in drug-free tests 1 d after CPP training (four pairings of 10 mg/kg cocaine with one context and four pairings of saline with a different context) increased Cdk5 activity, and levels of the Cdk5 activator p35 in basolateral but not central amygdala. We also found that basolateral (but not central) amygdala injections of the Cdk5 inhibitor beta-butyrolactone (100 ng/side) immediately (but not 6 h) after cocaine-context pairings during training prevented subsequent cocaine CPP expression. After training, acute basolateral (but not central) amygdala beta-butyrolactone injections immediately before testing prevented the expression of cocaine CPP; this effect was also observed on a second test performed 1 d later, suggesting an effect on reconsolidation of cocaine cue memories. In support, basolateral beta-butyrolactone injections, given immediately (but not 6 h) after a single exposure to the cocaine-paired context, prevented cocaine CPP expression 1 and 14 d after the injections. Results indicate that basolateral amygdala Cdk5 activity is critical for consolidation and reconsolidation of the memories of cocaine-associated environmental cues.

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Available from: Yan-Xue Xue, Jan 22, 2014
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    • "All of the drugs were freshly prepared and infused into the CA1 area of the dorsal hippocampus in a volume of 1.0 ␮l per side: propranolol (0 ␮g/ side, 0.3 ␮g/ side, or 1.0 ␮g/ side), RU486 (0 ␮g/ side, 0.3 ␮g/ side, or 1.0 ␮g/side, diluted in 10% DMSO in saline), Rp-cAMPS (0.5 ␮g/ side), U0126 (0.4 ␮g/ side, diluted in 10% DMSO in saline), and anisomycin (100 ␮g/␮l, diluted in saline; Moncada et al., 2011; Chai et al., 2014). The drugs were infused bilaterally over 1 min, and the injection needle was kept in place for an additional 1 min for drug diffusion (Lu et al., 2005; Li et al., 2010). Histology. "
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    ABSTRACT: Fear extinction forms a new memory but does not erase the original fear memory. Exposure to novelty facilitates transfer of short-term extinction memory to long-lasting memory. However, the underlying cellular and molecular mechanisms are still unclear. Using a classical contextual fear-conditioning model, we investigated the effect of novelty on long-lasting extinction memory in rats. We found that exposure to a novel environment but not familiar environment 1 h before or after extinction enhanced extinction long-term memory (LTM) and reduced fear reinstatement. However, exploring novelty 6 h before or after extinction had no such effect. Infusion of the β-adrenergic receptor (βAR) inhibitor propranolol and glucocorticoid receptor (GR) inhibitor RU486 into the CA1 area of the dorsal hippocampus before novelty exposure blocked the effect of novelty on extinction memory. Propranolol prevented activation of the hippocampal PKA-CREB pathway, and RU486 prevented activation of the hippocampal extracellular signal-regulated kinase 1/2 (Erk1/2)-CREB pathway induced by novelty exposure. These results indicate that the hippocampal βAR-PKA-CREB and GR-Erk1/2-CREB pathways mediate the extinction-enhancing effect of novelty exposure. Infusion of RU486 or the Erk1/2 inhibitor U0126, but not propranolol or the PKA inhibitor Rp-cAMPS, into the CA1 before extinction disrupted the formation of extinction LTM, suggesting that hippocampal GR and Erk1/2 but not βAR or PKA play critical roles in this process. These results indicate that novelty promotes extinction memory via hippocampal βAR- and GR-dependent pathways, and Erk1/2 may serve as a behavioral tag of extinction. Copyright © 2015 the authors 0270-6474/15/358308-14$15.00/0.
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    • "In this experiment, two groups of mice (N=7/group) underwent cocaine conditioned place preference as described above. Twenty-four hours following the test for cocaine place preference on day 9, half of the mice were confined to the previous cocaine-paired compartment in a drug-free state for 10 min to reactivate their cocaine-associated memories (Li et al. 2010; Wu et al. 2011) and were euthanized immediately at the end of the cue exposure. The other half were kept in their home cage and served as a no-reactivation control at the same time. "
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    • "Here, we will limit our analysis to those mechanisms previously covered in the present review. As noted above, CPP memory reconsolidation has been disrupted by translational inhibitors infused into various neural loci (Milekic et al., 2006; Li et al., 2008, 2010; Yang et al., 2011). "
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