The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization
The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization
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DOI：
10.1016/j.bbr.2012.10.042
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发表时间：
2013-02-15
影响因子：
2.7
通讯作者：
Anagnostaras, Stephan G.
中科院分区：
文献类型：
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作者：
Carmack, Stephanie A.;Kim, Jeesun S.;Anagnostaras, Stephan G.
最近，记忆和成瘾具有相似的神经基质的观点已被广泛接受。 N-甲基-D-天冬氨酸受体 (NMDAR) 是记忆突触模型的基石。本研究探讨了竞争性 NMDAR 拮抗剂 CPP 对诱导行为敏化和条件性可卡因位置偏好的影响。条件性位置偏好是一种寻求药物的联想记忆模型，而敏化是一种从随意使用到强迫使用过渡的非联想模型。得出三个主要发现：（1）CPP 和可卡因的共同给药改变了对可卡因的急性反应，表明两种药物之间存在直接相互作用； (2) NMDAR拮抗对行为敏化没有影响； (3) NMDAR 拮抗作用消除了条件性位置偏好。对支持 NMDAR 在致敏作用中作用的先前证据的回顾表明，NMDAR 拮抗剂直接干扰可卡因的精神兴奋作用，并且这种相互作用可能被误解为致敏作用的破坏。最后，我们认为成瘾会招募多种可塑性，而敏化则会招募不依赖于 NMDAR 的机制。 (C) 2012 Elsevier B.V. 保留所有权利。
Recently, the notion that memory and addiction share similar neural substrates has become widely accepted. N-methyl-D-aspartate receptors (NMDAR) are the cornerstones of synaptic models of memory. The present study examined the effect of the competitive NMDAR antagonist CPP on the induction of behavioral sensitization and conditioned place preference to cocaine. Conditioned place preference is an associative memory model of drug seeking, while sensitization is a non-associative model of the transition from casual to compulsive use. There were three principal findings: (1) co-administration of CPP and cocaine altered the acute response to cocaine, suggesting a direct interaction between the two drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3) NMDAR antagonism abolished conditioned place preference. A review of prior evidence supporting a role for NMDARs in sensitization suggests that NMDAR antagonists directly interfere with cocaine's psychostimulant effects, and this interaction could be misinterpreted as a disruption of sensitization. Finally, we suggest that addiction recruits multiple kinds of plasticity, with sensitization recruiting NMDAR-independent mechanisms. (C) 2012 Elsevier B.V. All rights reserved.