Retrodialysis of N/OFQ into the nucleus accumbens shell blocks cocaine-induced increases in extracellular dopamine and locomotor activity.
Retrodialysis of N/OFQ into the nucleus accumbens shell blocks cocaine-induced increases in extracellular dopamine and locomotor activity.
复制标题
N/OFQ 反渗析到伏隔核壳中可阻断可卡因诱导的细胞外多巴胺和运动活性的增加。
DOI：
10.1016/j.ejphar.2012.11.050
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发表时间：
2013
影响因子：
5
通讯作者：
Toll,Lawrence
中科院分区：
文献类型：
--
作者：
Vazquez-DeRose,Jacqueline;Stauber,Gregory;Khroyan,TalineV;Xie,XinminSimon;Zaveri,NurulainT;Toll,Lawrence
伤害感受肽 (N/OFQ) 与多种神经系统疾病有关，尤其是奖赏过程和药物滥用。脑室内注射后，N/OFQ 抑制伏隔核 (NAc) 中的细胞外多巴胺。本研究旨在探讨逆透析 N/OFQ 对可卡因诱导的 NAc 细胞外多巴胺水平增加以及自由活动大鼠的运动活动的影响。 NAc 壳中的 1.0μM、10μM 和 1mM N/OFQ 显着抑制 NAc 中可卡因诱导的多巴胺增加，而单独的 N/OFQ 对多巴胺水平没有显着影响。选择性 NOP 受体拮抗剂 SB612111 ([(–)-cis-1-Mmethyl-7-[[4-(2,6-二氯苯基)哌啶-1-基]甲基]-6,7,8,9-四氢-5H-苯并环庚烯-5-ol] 的共同递送逆转了 NAc 中可卡因诱导的多巴胺的 N/OFQ 抑制，表明这是一种 NOP 受体介导的使用一种新的系统来评估运动，我们测量了来自笼子的同时微透析的动物的各种运动活动，包括水平运动和站立行为，使用可卡因进行逆渗析影响了所有运动活动，最初显示对行为没有影响，但随着时间的推移，这些结果表明 N/OFQ 可以直接在 NAc 外壳中发挥作用，阻止可卡因诱导的细胞外活动增加。细胞外多巴胺和运动活性可以在 NAc 内解离，并且可能反映 NAc 外壳与核心区域的运动输出差异。这些研究证实了 NOP 受体在药物成瘾中的广泛参与，并进一步验证了 NOP 受体激动剂作为治疗药物成瘾的药物的效用。
Nociceptin (N/OFQ) has been implicated in a variety of neurological disorders, most notably in reward processes and drug abuse. N/OFQ suppresses extracellular dopamine in the nucleus accumbens (NAc) after intracerebroventricular injection. This study sought to examine the effects of retrodialyzed N/OFQ on the cocaine-induced increase in extracellular dopamine levels in the NAc, as well as locomotor activity, in freely moving rats. 1.0μM, 10μM, and 1mM N/OFQ, in the NAc shell, significantly suppressed the cocaine-induced dopamine increase in the NAc, while N/OFQ alone had no significant effect on dopamine levels. Co-delivery of the selective NOP receptor antagonist SB612111 ([(–)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol] reversed the N/OFQ suppression of cocaine-induced dopamine in the NAc, suggesting that this is an NOP receptor-mediated effect. Using a novel system to assess locomotion, we measured various motor activities of the animals with simultaneous microdialysis from the home cage. Cocaine produced an expected increase in total activity, including horizontal movement and rearing behavior. Retrodialysis of N/OFQ with cocaine administration affected all motor activities, initially showing no effect on behavior, but over time inhibiting cocaine-induced motor behaviors. These results suggest that N/OFQ can act directly in the NAc shell to block cocaine-induced increases in extracellular dopamine levels. Extracellular dopamine and locomotor activity can be dissociated within the NAc and may reflect motor output differences in shell versus core regions of the NAc. These studies confirm the widespread involvement of NOP receptors in drug addiction and further validate the utility of an NOP receptor agonist as a medication for treatment of drug addiction.