Depletion of Perineuronal Nets in the Amygdala to Enhance the Erasure of Drug Memories
Depletion of Perineuronal Nets in the Amygdala to Enhance the Erasure of Drug Memories
复制标题
耗尽杏仁核中的神经网络，以增强药物记忆的擦除。
DOI：
10.1523/jneurosci.5390-13.2014
复制
发表时间：
2014-05-07
影响因子：
5.3
通讯作者：
Lu, Lin
中科院分区：
文献类型：
--
作者：
Xue, Yan-Xue;Xue, Li-Fen;Lu, Lin
灭绝疗法被建议抑制药物线索的条件激励效应，以防止复发。然而，消退形成新的抑制性记忆，而不是消除原有的记忆痕迹，药物记忆总是会恢复。神经元周网（Perineuronalnets，PNNs）是大脑中中间神经元周围的一种特殊细胞外基质，已被认为是青少年大脑中允许突触可塑性的一种允许因素。软骨素酶ABC（ChABC）引起的PNNs的降解可能产生诱导的幼年样可塑性（iPlasticity），并促进成年大脑中的经验依赖性可塑性。本研究探讨了去除大鼠杏仁核PNNs对药物记忆消退的影响。我们发现，灭绝结合杏仁核内注射ChABC（0.01 U/侧）防止随后引发诱导恢复吗啡诱导和可卡因诱导，但不是食物诱导的条件性位置偏爱（CPP）。单独杏仁核内注射ChABC对吗啡诱导的CPP的保留、检索或再学习以及获得性食物诱导的CPP的储存没有影响。此外，我们发现，该程序有助于消除海洛因和可卡因寻求行为，并防止自发恢复和药物诱导的海洛因和可卡因寻求行为的恢复。我们还发现，PNNs降解结合灭绝的效果可能是由杏仁核中几种可塑性相关蛋白的增强介导的。总而言之，我们的研究结果表明，灭绝训练与杏仁核中的PNNs降解相结合可以消除药物记忆，并表明ChABC可能是预防复发的有吸引力的候选者。
Extinction therapy has been suggested to suppress the conditioned motivational effect of drug cues to prevent relapse. However, extinction forms a new inhibiting memory rather than erasing the original memory trace and drug memories invariably return. Perineuronal nets (PNNs) are a specialized extracellular matrix around interneurons in the brain that have been suggested to be a permissive factor that allows synaptic plasticity in the adolescent brain. The degradation of PNNs caused by chondroitinase ABC (ChABC) may generate induced juvenile-like plasticity (iPlasticity) and promote experience-dependent plasticity in the adult brain. In the present study, we investigated the effect of removing PNNs in the amygdala of rat on the extinction of drug memories. We found that extinction combined with intra-amygdala injections of ChABC (0.01 U/side) prevented the subsequent priming-induced reinstatement of morphine-induced and cocaine-induced, but not food-induced, conditioned place preference (CPP). Intra-amygdala injections of ChABC alone had no effect on the retention, retrieval, or relearning of morphine-induced CPP and storage of acquired food-induced CPP. Moreover, we found that the procedure facilitated the extinction of heroin-and cocaine-seeking behavior and prevented the spontaneous recovery and drug-induced reinstatement of heroin-and cocaine-seeking behavior. We also found that the effect of PNNs degradation combined with extinction may be mediated by the potentiation of several plasticity-related proteins in the amygdala. Altogether, our findings demonstrate that a combination of extinction training with PNNs degradation in the amygdala erases drug memories and suggest that ChABC may be an attractive candidate for the prevention of relapse.