Kraft M, Noailles P, Angulo J A
Department of Biological Sciences, Hunter College, City University of New York, 695 Park Avenue, New York, New York 10021, USA.
Ann N Y Acad Sci. 2001 Jun;937:121-31. doi: 10.1111/j.1749-6632.2001.tb03561.x.
To study the role of the neuropeptide substance P in modulating some of the effects of cocaine in the striatum, we administered cocaine to rats and measured preprotachykinin-A (PPT-A) messenger RNA and substance P peptide in the nigrostriatal pathway. We also measured the effect of a neurokinin-1 (NK-1) receptor antagonist on striatal cocaine-evoked dopamine overflow by in vivo microdialysis in freely moving animals. Acute administration of cocaine to naive rats (15 mg/kg of body weight) increased preprotachykinin-A mRNA levels in the dorsal and ventral aspects of the caudate putamen 4 hours after the intraperitoneal injection of cocaine. Concomitantly, in a separate group of animals, substance P peptide levels were decreased in the ventral caudate putamen and substantia nigra (38% below controls). In a separate experiment, infusion through the microdialysis probe of the neurokinin-1 receptor antagonist L-733,060 significantly decreased cocaine-evoked striatal dopamine overflow (approximately 50% inhibition at 30 minutes after cocaine administration). Taken together, these results suggest a direct role for substance P in the modulation of some of the actions of cocaine in the striatum of the rat brain.
为研究神经肽P物质在调节可卡因对纹状体的某些作用中的作用，我们给大鼠注射可卡因，并测量黑质纹状体通路中前速激肽原A（PPT-A）信使核糖核酸和P物质肽。我们还通过在自由活动动物体内进行微透析，测量了神经激肽-1（NK-1）受体拮抗剂对纹状体中可卡因诱发的多巴胺溢出的影响。给未接触过可卡因的大鼠急性注射可卡因（15毫克/千克体重），腹腔注射可卡因4小时后，尾状壳核背侧和腹侧的前速激肽原A信使核糖核酸水平升高。与此同时，在另一组动物中，腹侧尾状壳核和黑质中的P物质肽水平降低（比对照组低38%）。在另一项实验中，通过微透析探针注入神经激肽-1受体拮抗剂L-733,060，可显著降低可卡因诱发的纹状体多巴胺溢出（可卡因给药后30分钟时抑制约50%）。综合这些结果表明，P物质在调节可卡因对大鼠脑纹状体的某些作用中起直接作用。
