Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys
Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys
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DOI：
10.1007/s002130050054
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发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Howell, LL
中科院分区：
文献类型：
--
作者：
Czoty, PW;Justice, JB;Howell, LL
理论基础：可卡因的行为影响与大脑的多巴胺系统有关。将这一发现扩展到松鼠猴的神经化学研究，将增强我们对可卡因在非人类灵长类动物中的行为药理学的理解。目的：通过微透析实验研究可卡因和选择性多巴胺摄取抑制剂GBR-12909对清醒松鼠猴尾状核细胞外多巴胺的影响。方法：在标准松鼠脑图谱上，用立体定位仪将引导管植入4只猕猴的尾状核内。所有受试者均通过磁共振成像确认了准确的探头位置。结果：总的来说，结果支持重复测量设计的可行性。在多次实验中，通过测量一致的多巴胺及其代谢物的基础水平，观察钾诱导的多巴胺释放，以及通过GFAP(胶质纤维酸性蛋白)免疫化学评估没有显著的胶质细胞增殖，支持了重复插入探针后组织完整性的稳定性。此外，在几次实验中，当多个探针位于同一解剖位置时，药物效应峰值和作用时间进程相似。可卡因(1.0毫克/公斤肌肉注射)和12909英镑(3.0mg.kgI.M.)细胞外多巴胺水平升高到基础水平的大约300%，但与可卡因相比，GBR 12909产生的升高更慢、更持久。结论：通过对同一解剖部位的重复取样，结果验证了微透析在清醒灵长类动物中的应用，并证明了在给予多巴胺摄取抑制剂后细胞外多巴胺的有序变化。
Rationale: The behavioral effects of cocaine have been linked to brain dopamine systems. Extending the findings to neurochemical studies in the squirrel monkey would enhance our understanding of the behavioral pharmacology of cocaine in nonhuman primates. Objectives: The present studies characterized the effects of cocaine and the selective dopamine uptake inhibitor GBR 12909 on extracellular dopamine in the caudate nucleus of awake squirrel monkeys through microdialysis experiments. Methods: Guide cannulae were implanted in the caudate nucleus of four monkeys using a stereotaxic apparatus and coordinates obtained from a standard squirrel monkey brain atlas. Accurate probe placement was confirmed in all subjects with magnetic resonance imaging, Results: Collectively, the results support the feasibility of a repeated-measures design. Stability of tissue integrity after repeated probe insertion was supported by measurement of consistent basal levels of dopamine and its metabolites across several experiments, observation of potassium-induced dopamine release and absence of significant glial proliferation as assessed by GFAP (glial fibrillary acidic protein) immunochemistry. Moreover, peak drug effects and time-course of action were similar when multiple probes were positioned in the same anatomical site over several experiments. Cocaine (1.0 mg/kg i.m.) and GBR 12909 (3.0 mg/kg i.m.) elevated extracellular dopamine to approximately 300% of basal levels, but GBR 12909 produced a slower, more sustained elevation than cocaine. Conclusions: The results validate the use of microdialysis in awake primates using repeated sampling of the same anatomical site and demonstrate orderly changes in extracellular dopamine following administration of dopamine uptake inhibitors.