Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA.
Psychopharmacology (Berl). 2013 Apr;226(4):707-19. doi: 10.1007/s00213-012-2793-y. Epub 2012 Jul 25.
Environmental stimuli or contexts previously associated with rewarding drugs contribute importantly to relapse among addicts, and research has focused on neurobiological processes maintaining those memories. Much research shows contributions of cell surface receptors and intracellular signaling pathways in maintaining associations between rewarding drugs (e.g., cocaine) and concurrent cues/contexts; these memories can be degraded at the time of their retrieval through reconsolidation interference. Much less studied is the consolidation of drug-cue memories during their acquisition.
The present experiments use the cocaine-conditioned place preference (CPP) paradigm in rats to directly compare, in a consistent setting, the effects of N-methyl-D-aspartate (NMDA) glutamate receptor antagonists MK-801 and memantine on the consolidation and reconsolidation of cocaine-cue memories.
For the consolidation studies, animals were systemically administered MK-801 or memantine immediately following training sessions. To investigate the effects of these NMDA receptor antagonists on the retention of previously established cocaine-cue memories, animals were systemically administered MK-801 or memantine immediately after memory retrieval.
Animals given either NMDA receptor antagonist immediately following training sessions did not establish a preference for the cocaine-paired compartment. Post-retrieval administration of either NMDA receptor antagonist attenuated the animals' preference for the cocaine-paired compartment. Furthermore, animals given NMDA receptor antagonists post-retrieval showed a blunted response to cocaine-primed reinstatement.
Using two distinct NMDA receptor antagonists in a common setting, these findings demonstrate that NMDA receptor-dependent processes contribute both to the consolidation and reconsolidation of cocaine-cue memories, and they point to the potential utility of treatments that interfere with drug-cue memory reconsolidation.
先前与奖赏性药物相关联的环境刺激或环境背景，对成瘾者的复吸起着重要作用，而研究则主要集中在维持这些记忆的神经生物学过程上。大量研究表明，细胞表面受体和细胞内信号通路在维持奖赏性药物（例如可卡因）与同时出现的线索/环境之间的关联中起着重要作用；这些记忆可以在它们被检索时通过再巩固干扰而被破坏。在获得药物线索记忆的过程中，药物线索记忆的巩固过程研究得较少。
本实验使用大鼠可卡因条件性位置偏爱（CPP）范式，在一个一致的环境中，直接比较 N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂 MK-801 和美金刚胺对可卡因-线索记忆的巩固和再巩固的影响。
在巩固研究中，动物在训练后立即接受 MK-801 或美金刚胺的全身给药。为了研究这些 NMDA 受体拮抗剂对先前建立的可卡因-线索记忆的保留的影响，动物在记忆检索后立即接受 MK-801 或 memantine 的全身给药。
动物在接受训练后立即给予 NMDA 受体拮抗剂，不会对可卡因配对的隔间产生偏好。在检索后给予 NMDA 受体拮抗剂，会减弱动物对可卡因配对隔间的偏好。此外，在检索后给予 NMDA 受体拮抗剂的动物对可卡因引发的复吸反应迟钝。
在一个共同的环境中使用两种不同的 NMDA 受体拮抗剂，这些发现表明 NMDA 受体依赖性过程既有助于可卡因-线索记忆的巩固，也有助于可卡因-线索记忆的再巩固，并且它们指出了干扰药物-线索记忆再巩固的治疗方法的潜在效用。
