R.S. Dow Neurobiology, Legacy Research Institute, Portland, Oregon 97232.
Program in Neuroscience, Washington State University, Vancouver, Washington 98686.
J Neurosci. 2024 Aug 21;44(34):e0468242024. doi: 10.1523/JNEUROSCI.0468-24.2024.
The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. The output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets. We previously showed that treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Furthermore, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.
内侧前额叶皮层（mPFC）是人类可卡因复吸和可卡因使用障碍啮齿动物模型中复吸的主要贡献者。mPFC 的输出受到含有 parvalbumin（PV）的快速放电中间神经元的强烈调节，其中大多数被周围神经网包围。我们之前的研究表明，软骨素酶 ABC（ABC）治疗可减少可卡因条件性位置偏好记忆的巩固和再巩固。然而，自我给药记忆更难破坏。在这里，我们在雄性大鼠中报告说，mPFC 中的 ABC 治疗减弱了可卡因自我给药记忆的巩固并阻止了其再巩固。然而，当大鼠接受新的但不是熟悉的检索会话时，再巩固被阻止。此外，在记忆检索之前而不是之后给予 ABC 治疗会阻止再巩固。相同的治疗并未改变蔗糖记忆，表明其对可卡因诱导的记忆具有特异性。在未接受治疗的大鼠中，mPFC 中的 ABC 治疗改变了 PV 强度和细胞放电特性的水平。在新的检索会话期间，来自 mPFC 和背侧海马（dHIP）的体内记录显示，ABC 阻止了与奖励相关的高频振荡的增加以及 dHIP 和 mPFC 之间这些振荡的同步性。总之，这是第一项研究表明，当与引发 dHIP 和 mPFC 之间耦合的新检索会话结合使用时，ABC 治疗会破坏原始记忆的再巩固。ABC 治疗后的这种耦合可能是破坏可卡因记忆再巩固和减少复发的基本特征。
