Effect of the endogenous κ opioid agonist dynorphin A(1–17) on cocaine-evoked increases in striatal dopamine levels and cocaine-induced place preference in C57BL/6J mice
Effect of the endogenous κ opioid agonist dynorphin A(1–17) on cocaine-evoked increases in striatal dopamine levels and cocaine-induced place preference in C57BL/6J mice
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DOI：
10.1007/s00213-003-1688-3
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发表时间：
2004-01
影响因子：
3.4
通讯作者：
Yong Zhang;E. Butelman;S. Schlussman;A. Ho;M. Kreek
中科院分区：
文献类型：
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作者：
Yong Zhang;E. Butelman;S. Schlussman;A. Ho;M. Kreek
合成κ阿片受体激动剂对可卡因诱导的奖赏的影响已经在大鼠中进行了广泛的研究，但是相对较少的研究使用内源性κ激动剂强啡肽A（1-17）。对C57 BL/6 J小鼠条件性位置偏爱形成和自发活动增加的影响。方法将引导插管植入尾壳核后，使小鼠从手术中恢复4-5天。在第一项研究中，强啡肽A（0，1，2，4.4 nmol）注入尾壳核和多巴胺水平测定在该脑区的体内微透析。然后，强啡肽A（4.4 nmol）对15 mg/kg可卡因腹腔注射引起的多巴胺水平增加的影响也用体内微透析法测定。第三个实验研究的效果强啡肽A（4.4 nmol）对条件性位置偏爱和运动诱导的15 mg/kg cocaine. ResultsDynophin A显着降低基础多巴胺水平在一个剂量依赖性的方式超过60%，在最高剂量，这种效果被完全阻断预注射的κ-阿片受体拮抗剂去甲-BNI（10 mg/kg）。最高剂量的强啡肽（4.4 nmol）可阻断15 mg/kg可卡因诱导的多巴胺水平升高、条件性位置偏好的形成和运动减弱。结论阻断可卡因诱导的纹状体多巴胺升高可能有助于强啡肽的能力，以防止可卡因诱导的条件性位置偏好的发展并减弱运动活动的增加。
RationaleEffects of synthetic kappa opioid receptor agonists on cocaine-induced reward have been studied extensively in rats but relatively few studies have used the endogenous kappa agonist dynorphin A(1–17).ObjectivesThree studies were conducted to examine the effect of the natural sequence dynorphin on cocaine-induced increases in dopamine, on the formation of conditioned place preference and on increases in locomotor activity in C57BL/6 J mice.MethodsAfter implantation of guide cannulae into the caudate putamen, mice were allowed 4–5 days to recover from surgery. In the first study, dynorphin A (0, 1, 2, 4.4 nmol) was infused into the caudate putamen and dopamine levels were measured by in vivo microdialysis in that brain region. Then, the effect of dynorphin A (4.4 nmol) on increases in dopamine levels induced by 15 mg/kg cocaine i.p. was also measured with in vivo microdialysis. The third experiment examined the effect of dynorphin A (4.4 nmol) on conditioned place preference and locomotion induced by 15 mg/kg cocaine.ResultsDynorphin A significantly decreased basal dopamine levels in a dose-dependent manner by more than 60% at the highest dose, and this effect was completely blocked by pre-injection of the kappa-opioid receptor antagonist nor-BNI (10 mg/kg). The highest dose of dynorphin (4.4 nmol) blocked increases in dopamine levels, the formation of conditioned place preference and attenuated locomotion induced by 15 mg/kg cocaine.ConclusionThe blockade of the cocaine-induced rise in striatal dopamine may contribute to both dynorphin’s ability to prevent the development of cocaine-induced conditioned place preference and to attenuate the increase in locomotor activity.