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.

译文

最近,记忆和成瘾共享相似神经底物的观念已被广泛接受。N-甲基-d-天冬氨酸受体 (NMDAR) 是记忆突触模型的基石。本研究检查了竞争性NMDAR拮抗剂CPP对可卡因的行为敏化和条件性位置偏好的诱导作用。条件性场所偏好是寻求药物的联想记忆模型,而敏化是从随意使用到强迫使用的非联想模型。有三个主要发现 :( 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拮抗作用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NMDARs在致敏作用中的先前证据的审查表明,NMDAR拮抗剂直接干扰可卡因的精神刺激作用,这种相互作用可能被误解为致敏的破坏。最后,我们建议成瘾招募多种可塑性,并通过敏感性招募与NMDAR无关的机制。

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