Frank Stefanie Th, Krumm Bertram, Spanagel Rainer
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Synapse. 2008 Apr;62(4):243-52. doi: 10.1002/syn.20489.
A meta-analysis was conducted on data obtained from published articles which used in vivo microdialysis to assess dose-response curves of cocaine on dopamine (DA) overflow within the nucleus accumbens (NAC). Different experimental and biological parameters such as route of administration (ip, sc, iv, local), rat and mouse strains, gender, age aspects, and regions cannulated (NAC core and shell) were considered. Data from 116 experiments involving 833 animals (out of 266 publications) fulfilled our selection criteria and were analyzed in relation to absolute basal DA levels, the maximum peak of DA overflow (peak [%] baseline) and the time when this peak (peak time) occurred. Our meta-analysis revealed that absolute basal DA levels lie at 2.39 nM (median of all experiments) and that cocaine-induced DA overflow in the NAC is significantly enhanced in a linear dose-response fashion within the applied dose range as the regression function increases following either iv or ip administration. Peak time was reached fastest in iv experiments and slowest following local application. Furthermore, it was shown in ip experiments that the higher the dose, the longer it took to reach the zenith. Results from the NAC shell region displayed greater DA overflow as compared with the NAC core. DA overflow properties following cocaine treatment in mice did not differ from that in rats. Thus, neither species differences nor other biological factors such as, age, gender, and rat/mouse strain have a pronounced impact on cocaine-induced DA overflow. Technical parameters of the microdialysis procedure such as calcium concentration of the perfusion medium and collected sample amount have also no significant effect in terms of DA overflow properties (peak [%] baseline and peak time) following cocaine treatment. In conclusion, these data may be deemed useful for textbook knowledge and a better comparability of data given by the generalization of already existing data as well as for investigators in maximizing the effect of cocaine-induced DA overflow. Finally, this study examplifies how meta- analyses may be applied to a wide range of data within the field of neurochemistry.
对已发表文章中的数据进行了一项荟萃分析，这些文章使用体内微透析来评估可卡因对伏隔核（NAC）内多巴胺（DA）溢出的剂量反应曲线。考虑了不同的实验和生物学参数，如给药途径（腹腔注射、皮下注射、静脉注射、局部注射）、大鼠和小鼠品系、性别、年龄因素以及插管区域（NAC核心和壳）。来自116项实验（涉及266篇出版物中的833只动物）的数据符合我们的选择标准，并根据绝对基础DA水平、DA溢出的最大峰值（峰值[％]基线）以及该峰值出现的时间（峰值时间）进行了分析。我们的荟萃分析表明，绝对基础DA水平为2.39 nM（所有实验的中位数），并且在静脉注射或腹腔注射后，随着回归函数的增加，在所应用的剂量范围内，可卡因诱导的NAC中DA溢出以线性剂量反应方式显著增强。静脉注射实验中峰值时间最快达到，局部应用后最慢。此外，腹腔注射实验表明，剂量越高，达到峰值所需的时间越长。与NAC核心相比，NAC壳区域的结果显示出更大的DA溢出。可卡因治疗后小鼠的DA溢出特性与大鼠没有差异。因此，物种差异以及其他生物学因素，如年龄、性别和大鼠/小鼠品系，对可卡因诱导的DA溢出没有明显影响。微透析程序的技术参数，如灌注介质的钙浓度和收集的样品量，对可卡因治疗后的DA溢出特性（峰值[％]基线和峰值时间）也没有显著影响。总之，这些数据对于教科书知识以及通过对现有数据的概括提高数据的可比性可能是有用的，并且对于研究人员最大化可卡因诱导的DA溢出的效果也可能是有用的。最后，这项研究举例说明了荟萃分析如何应用于神经化学领域的广泛数据。
