Department of Integrative Physiology and Neuroscience, Washington State University College of Veterinary Medicine, Pullman, WA, USA.
Department of Integrative Physiology and Neuroscience, Washington State University College of Veterinary Medicine, Pullman, WA, USA; Washington State University Alcohol and Drug Abuse Research Program, Pullman, WA, USA.
Neuropharmacology. 2024 Mar 15;246:109832. doi: 10.1016/j.neuropharm.2023.109832. Epub 2024 Jan 3.
Memory reconsolidation is a process by which labile drug memories are restabilized in long-term memory stores, permitting their enduring control over drug-seeking behaviors. In the present study, we investigated the involvement of the dorsal raphé nuclei (DRN) in cocaine-memory reconsolidation. Sprague-Dawley rats (male, female) were trained to self-administer cocaine in a distinct environmental context to establish contextual drug memories. They then received extinction training in a different context. Next, the rats were re-exposed to the cocaine-predictive context for 15 min to reactivate their cocaine memories or remained in their home cages (no-reactivation control). Memory reactivation was sufficient to increase c-Fos expression, an index of neuronal activation, in the DRN, but not in the median raphé nuclei, during reconsolidation, compared to no reactivation. To determine whether DRN neuronal activity was necessary for cocaine-memory reconsolidation, rats received intra-DRN baclofen plus muscimol (BM; GABA agonists) or vehicle microinfusions immediately after or 6 h after a memory reactivation session conducted with or without lever access. The effects of DRN functional inactivation on long-term memory strength, as indicated by the magnitude of context-induced cocaine seeking, were assessed 72 h later. Intra-DRN BM treatment immediately after memory reactivation with or without lever access attenuated subsequent context-induced cocaine-seeking behavior, independent of sex. Conversely, BM treatment in the adjacent periaqueductal gray (PAG) immediately after memory reactivation, or BM treatment in the DRN 6 h after memory reactivation, did not alter responding. Together, these findings indicate that the DRN plays a requisite role in maintaining cocaine-memory strength during reconsolidation.
记忆再巩固是一个不稳定的药物记忆在长期记忆库中重新稳定的过程，使其能够持久地控制药物寻求行为。在本研究中，我们研究了背侧中缝核（DRN）在可卡因记忆再巩固中的作用。雄性和雌性 Sprague-Dawley 大鼠接受可卡因自我给药训练，在特定环境背景下建立环境药物记忆。然后，它们在不同的环境中接受消退训练。接下来，老鼠重新暴露在可卡因预测环境中 15 分钟，以重新激活可卡因记忆，或留在它们的家笼中（无再激活对照）。与无再激活相比，记忆再激活足以增加 DRN 中的 c-Fos 表达，这是神经元激活的一个指标，但不会增加中缝核中的 c-Fos 表达。为了确定 DRN 神经元活动是否是可卡因记忆再巩固所必需的，大鼠在记忆再激活后立即或 6 小时后接受 DRN 内巴氯芬加毒蕈碱（BM；GABA 激动剂）或载体微注射，无论是否有杠杆接入。72 小时后，根据环境诱发可卡因寻求的程度评估 DRN 功能失活对长期记忆强度的影响。记忆再激活后立即接受 DRN 内 BM 治疗，无论是否有杠杆接入，均可减弱随后的环境诱发可卡因寻求行为，而与性别无关。相反，记忆再激活后立即在相邻的中脑导水管周围灰质（PAG）中给予 BM 治疗，或记忆再激活后 6 小时在 DRN 中给予 BM 治疗，均不会改变反应。这些发现表明，DRN 在再巩固过程中维持可卡因记忆强度方面起着必要的作用。
