Afanas'ev I I, Anderzhanova E A, Kudrin V S, Rayevsky K S
Laboratory of Neurochemical Pharmacology, Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiyskaya str., 8, Moscow, 125315 Russia.
Pharmacol Biochem Behav. 2001 Jul-Aug;69(3-4):653-8. doi: 10.1016/s0091-3057(01)00574-3.
Microdialysis technique was used to compare the effects of four repeated intraperitoneal administrations of two psychostimulant drugs, D-amphetamine and sydnocarb, at the equimolar doses 5 and 23.8 mg/kg, respectively, on the extracellular level of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and hydroxyl radicals (.OH) in the dorsal striatum of freely moving 3-month-old male Wistar rats 250-300 g in weight. D-amphetamine caused immediate increase of DA concentration up to 950% with quick decline towards baseline values thereafter, followed by much less increase after further injections. Sydnocarb elicited moderate elevation in DA level achieving 400% after the fourth injection. D-amphetamine induced deep decrease in DOPAC concentration, while sydnocarb caused its increase after the first and second dosing. Both drugs enhanced generation of .OH, the effect of D-amphetamine was more pronounced. D-Amphetamine induced more intensive stereotyped behavior in rats compare to sydnocarb. It is concluded that the psychostimulant action of sydnocarb is accompanied by facilitation of the central dopaminergic transmission in rat neostriatum and followed by less pronounced neurotoxic effect than that of D-amphetamine.
采用微透析技术,分别以等摩尔剂量5毫克/千克和23.8毫克/千克腹腔注射两种精神兴奋药——D-苯丙胺和西诺卡宾,对体重250-300克、3月龄自由活动的雄性Wistar大鼠的背侧纹状体细胞外多巴胺(DA)、3,4-二羟基苯乙酸(DOPAC)和羟自由基(·OH)水平的影响进行比较。D-苯丙胺使DA浓度立即升高至950%,之后迅速降至基线值,后续注射后升高幅度小得多。西诺卡宾使DA水平适度升高,第四次注射后达到400%。D-苯丙胺使DOPAC浓度大幅降低,而西诺卡宾在首次和第二次给药后使其升高。两种药物均增强了·OH的生成,D-苯丙胺的作用更明显。与西诺卡宾相比,D-苯丙胺诱导大鼠出现更强烈的刻板行为。得出结论:西诺卡宾的精神兴奋作用伴随着大鼠新纹状体中中枢多巴胺能传递的促进,且神经毒性作用比D-苯丙胺弱。