Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice.
Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice.
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DOI：
10.1007/s00213-008-1432-0
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发表时间：
2009-05
影响因子：
3.4
通讯作者：
Xi, Zheng-Xiong
中科院分区：
文献类型：
--
作者：
Li, Xia;Hoffman, Alexander F.;Peng, Xiao-Qing;Lupica, Carl R.;Gardner, Eliot L.;Xi, Zheng-Xiong
大麻素CB 1受体缺失对可卡因作用的影响存在争议。这部分是基于具有CD 1遗传背景的CB 1受体敲除（CB 1 −/−）小鼠的发现。在本研究中，我们使用具有C57 BL/6 J遗传背景的CB 1 −/−小鼠进一步研究CB 1受体在可卡因作用中的作用。使用AccuScan运动室评估运动活性。通过体内微透析和伏隔核（NAc）快速扫描循环伏安法测量脑细胞外多巴胺（DA）水平。与野生型（CB 1 +/+）同窝出生的小鼠相比，CB 1 −/−小鼠的运动和细胞外DA的基础水平以及可卡因增强的运动和细胞外DA显著降低。基础和可卡因增强DA的减少似乎与基础DA释放的减少有关，而不是DA清除率的增加，如脑切片中的快速扫描循环伏安法所示。SR 141716对CB 1受体的药理学阻断抑制了CB 1 +/+小鼠的运动和NAc DA释放。目前的研究结果表明，CB 1受体在介导可卡因的行为和神经化学作用的重要作用。
Effect of cannabinoid CB1 receptor deletion on cocaine’s actions is controversial. This is partly based on findings in CB1-receptor-knockout (CB1−/−) mice with CD1 genetic background. In the present study, we used CB1−/− mice with a C57BL/6J genetic background to further investigate the role of CB1 receptors in cocaine’s action. Locomotor activity was assessed using AccuScan locomotor chambers. Brain extracellular dopamine (DA) levels were measured by in vivo microdialysis and by fast-scan cyclic voltammetry in the nucleus accumbens (NAc). CB1−/− mice displayed a significant reduction in basal levels of locomotion and extracellular DA, as well as in cocaine-enhanced locomotion and extracellular DA, as compared to their wild-type (CB1+/+) littermates. The reduction in basal and cocaine-enhanced DA appears to be related to a reduction in basal DA release, not to an increase in DA clearance, as indicated by fast-scan cyclic voltammetry in brain slices. Pharmacological blockade of CB1 receptors by SR141716 inhibited locomotion and NAc DA release in CB1+/+ mice. The present findings suggest an important role for CB1 receptors in mediating cocaine’s behavioral and neurochemical effects.
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影响因子：
25
作者：
Giuffrida, A;Parsons, LH;Piomelli, D
通讯作者：
Piomelli, D
影响因子：
56.9
作者：
Ledent, C;Valverde, O;Parmentier, M
通讯作者：
Parmentier, M
影响因子：
2.3
作者：
Cornish, JL;Kalivas, PW
通讯作者：
Kalivas, PW
影响因子：
5.3
作者：
Köfalvi, A;Rodrigues, RJ;Sperlágh, B
通讯作者：
Sperlágh, B
影响因子：
3.3
作者：
Julian, MD;Martin, AB;Garcia-Segura, LM
通讯作者：
Garcia-Segura, LM