Cocaine use disorder develops in part due to the strong associations formed between drugs and the stimuli associated with drug use. Recently, treatment strategies including manipulations of drug-associated memories have been investigated, and the possibility of interfering with N-methyl-d-aspartate (NMDA)-mediated neurotransmission may represent an important option. The aim of this study was to examine the significance of the NMDA receptor subunit GluN2B at the molecular level (the expression of the GluN2B subunit, the Grin2B gene and the association of GluN2B with postsynaptic density protein 95 (PSD95)) in the brain structures of rats with a history of cocaine self-administration after i) cocaine abstinence with extinction training or ii) cocaine abstinence without instrumental tasks, as well as at the pharmacological level (peripheral or intracranial administration of CP 101,606, a GluN2B subunit antagonist during the cocaine- or cue-induced reinstatement). The GluN2B subunit levels and the GluN2B/PSD95 complex levels were either increased in the ventral hippocampus (vHIP) with higher levels of Grin2B gene expression in the HIP or decreased in the dorsal striatum (dSTR) after cocaine abstinence with extinction training. Moreover, CP 101,606, a GluN2B subunit antagonist, administered peripherally, attenuated the reinstatement of active lever presses induced by a priming dose of cocaine or by drug-associated conditioned stimuli, while injection into the vHIP reduced the cocaine- or cue with the subthreshold dose of cocaine-induced reinstatement. In cocaine abstinence without instrumental tasks, an increase in the GluN2B subunit levels and the level of the GluN2B/PSD95 complex in the dSTR was observed in rats that had previously self-administered cocaine. In conclusion, cocaine abstinence with extinction training seems to be associated with the up-regulation of the hippocampal GluN2B subunits, which seems to control cocaine-seeking behavior.

可卡因使用障碍的发展部分是由于药物与与药物使用相关的刺激之间形成的强烈关联。最近，已经研究了包括操纵药物相关记忆在内的治疗策略，并且干扰N-甲基-d-天冬氨酸 (NMDA) 介导的神经传递的可能性可能是一个重要的选择。本研究的目的是在分子水平上检查 NMDA 受体亚基 GluN2B 的意义（GluN2B 亚基的表达，Grin2B基因和 GluN2B 与突触后密度蛋白 95 (PSD95)) 在有可卡因自我给药史的大鼠脑结构中的关联，在 i) 可卡因戒断与消退训练或 ii) 可卡因戒断没有工具任务，以及在药理水平（CP 101,606 的外周或颅内给药，一种 GluN2B 亚基拮抗剂在可卡因或提示诱导的恢复期间）。GluN2B 亚基水平和 GluN2B/PSD95 复合物水平在腹侧海马 (vHIP) 中增加，Grin2B水平较高可卡因戒断和消退训练后，HIP 中的基因表达或背侧纹状体 (dSTR) 中的基因表达降低。此外，外周给药的 GluN2B 亚基拮抗剂 CP 101,606 减弱了由初始剂量的可卡因或药物相关条件刺激诱导的主动杠杆按压的恢复，而注射到 vHIP 中则减少了阈下剂量的可卡因或提示可卡因诱导的恢复。在没有工具性任务的可卡因戒断中，在先前自行服用可卡因的大鼠中观察到 dSTR 中 GluN2B 亚基水平和 GluN2B/PSD95 复合物水平的增加。总之，灭绝训练的可卡因戒断似乎与海马 GluN2B 亚基的上调有关，这似乎控制了可卡因寻求行为。