Activation of Epac in the BLA disrupts reconsolidation and attenuates heroin‐seeking behaviour

作者：Shihao Huang, Cuijie Shi, Fanglin Liu, Yue Si, Dan Shen, Liping Yang, Yujun Gao, Yiwei Liao · 发表于：Addiction Biology · 年份：2023 · DOI：10.1111/adb.13330 · 被引用次数：5 · 研究领域：Memory and Neural Mechanisms、Receptor Mechanisms and Signaling、Neuroscience and Neuropharmacology Research

The susceptibility to drug cravings evoked by stimuli poses a formidable hurdle in the treatment of addiction and the prevention of relapse. Pharmacological interventions targeting drug-associated memories hold promise for curbing relapse by impeding the process of memory reconsolidation, predominantly governed by cAMP signalling. Exchange Protein Activated by cAMP (Epac) serves as a distinctive mediator of cAMP signalling, which has been implicated in reinforcing the effects of cocaine and facilitating the acquisition. Nonetheless, the role of Epac in heroin-related memory and the subsequent seeking behaviour remains enigmatic. In this study, we explored the impact of Epac activation on the reconsolidation process of drug-related memories associated with heroin self-administration. Over the course of 10 consecutive days, rats underwent training, wherein they acquired the behaviour of nose poking to obtain heroin accompanied by a tone + light cue. This nose-poking behaviour was subsequently extinguished when heroin infusion and cue presentation were discontinued. Subsequently, we administered 8-pCPT-cAMP (8-CPT), an Epac-specific activator, into the basolateral amygdala at various time points, either in the presence or absence of a conditioned stimulus. Our findings demonstrate that administering 8-CPT immediately after memory retrieval effectively reduces cue- and heroin-induced reinstatement, with the observed effects persisting significantly for a minimum of 28 days. Howev...