Involvement of reactive oxygen species in cocaine-taking behaviors in rats.
Involvement of reactive oxygen species in cocaine-taking behaviors in rats.
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DOI：
10.1111/adb.12159
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发表时间：
2015-07
影响因子：
3.4
通讯作者：
Kim HY
中科院分区：
文献类型：
--
作者：
Jang EY;Ryu YH;Lee BH;Chang SC;Yeo MJ;Kim SH;Folsom RJ;Schilaty ND;Kim KJ;Yang CH;Steffensen SC;Kim HY
活性氧（ROS）已被牵连在重复可卡因暴露后的行为敏化的发展。我们假设，增加ROS可卡因暴露后，将作为信号分子在中脑边缘多巴胺（DA）系统，这可能在介导可卡因的增强效应中发挥重要作用。本研究的目的是评估可卡因对脑代谢活动的增强作用以及ROS清除剂对可卡因自我给药行为、可卡因诱导的中脑核（NAc）中ROS产生和可卡因增强NAc中DA释放的影响。代谢神经活动监测温度和氧化应激增加NAC可卡因暴露后。在治疗前或治疗后全身给予ROS清除剂N-叔丁基-α-苯基硝酮（PBN）或4-羟基-2，2，6，6-四甲基哌啶-1-氧基（TEMPOL），可显著降低可卡因自我给药，而不影响食物摄入。TEMPOL注入NAc抑制可卡因自我管理。增加的氧化应激主要是神经元，但不是星形胶质细胞，小胶质细胞或少突胶质细胞，在NAC的大鼠自我管理可卡因。TEMPOL显着衰减可卡因诱导的增强DA释放的NAC，与盐水对照。TEMPO对DA转运体抑制剂GBR 12909产生的DA释放增强没有影响。总之，这些发现表明，在NAc神经元的ROS产生的增强有助于可卡因的增强作用。
Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-administration behavior, cocaine-induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), either pre- or post-treatment, significantly decreased cocaine self-administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self-administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self-administering cocaine. TEMPOL significantly attenuated cocaine-induced enhancement of DA release in the NAc, compared to saline controls. TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine.