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 medial 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_B/A 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.

记忆重新巩固是一个过程，通过这个过程，不稳定的药物记忆在长期记忆存储中重新稳定，从而使他们能够持久地控制寻求药物的行为。在本研究中，我们研究了中缝背核（DRN）在可卡因记忆重建中的作用。Sprague-Dawley 大鼠（雄性、雌性）被训练在不同的环境背景下自我施用可卡因，以建立背景药物记忆。然后他们在不同的环境中接受灭绝训练。接下来，将老鼠重新暴露在可卡因预测环境中 15 分钟，以重新激活它们的可卡因记忆，或者留在它们的笼子里（无重新激活对照）。与没有重新激活相比，在重新巩固过程中，记忆重新激活足以增加 DRN 中的 c-Fos 表达（神经元激活指数），但不会增加中缝核中的表达。为了确定 DRN 神经元活动是否是可卡因记忆重新巩固所必需的，大鼠在使用或不使用杠杆访问进行记忆重新激活会话后立即或 6 小时后立即接受 DRN 内巴氯芬加蝇蕈醇（BM；GABA B _/A激动剂）或载体微输注。72 小时后，评估 DRN 功能失活对长期记忆强度的影响，如情境诱导的可卡因寻求程度所示。记忆重新激活后立即进行 DRN 内 BM 治疗，无论有或没有杠杆访问，都会减弱随后的环境诱发的可卡因寻求行为，与性别无关。相反，记忆重新激活后立即在邻近导水管周围灰质 (PAG) 进行 BM 治疗，或记忆重新激活后 6 小时在 DRN 中进行 BM 治疗，不会改变反应。总之，这些发现表明 DRN 在重新巩固过程中维持可卡因记忆强度方面发挥着必要的作用。