Departamento de Farmacología (IFEC - CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
Eur J Pharmacol. 2010 Mar 25;630(1-3):79-83. doi: 10.1016/j.ejphar.2009.12.029. Epub 2010 Jan 4.
GM1 pretreatment enhanced the rewarding properties of cocaine as assessed in the conditioned place preference paradigm. This effect was shown by the lower dosage of cocaine necessary to induce conditioning compared with rats receiving cocaine alone, as well as by the fewer number of sessions necessary to induce place preference. GM1 pretreatment did not modify the plasma level of cocaine, but it induced a significant increase in the brain cocaine level compared with animals receiving cocaine alone. In order to evaluate the possibility that GM1 pretreatment may alter the pharmacokinetic parameters of cocaine, the brain and plasma esterase activities, the plasma bound/free cocaine ratio and the brain blood barrier permeability to i.v. Evans Blue administration were assessed. None of these parameters was modified by the GM1 administration. In addition, GM1 (100microM) did not alter the dopamine transporter inhibition induced by cocaine (10(-7)-10(-5)M), as determined by the uptake of [(3-)H]-dopamine in the microsacs of nucleus accumbens. In conclusion, GM1 pretreatment, which did not have any effect per se, increased the rewarding effect of cocaine, a phenomenon correlated with a significant increase in the brain cocaine levels. The different pharmacokinetic parameters evaluated, as well as the inhibitory effect of cocaine on the dopamine transporter, were not modified by GM1, but it modifies the brain cocaine disposition. Thus, the mechanisms by which GM1 enhanced the rewarding effects of cocaine merit further study.
GM1 预处理增强了可卡因的奖赏特性，这可以通过条件性位置偏爱范式来评估。与单独给予可卡因的大鼠相比，GM1 预处理所需的可卡因剂量更低，以及诱导位置偏好所需的次数更少，这表明了这种效果。GM1 预处理不会改变可卡因的血浆水平，但与单独给予可卡因的动物相比，GM1 预处理会显著增加大脑中的可卡因水平。为了评估 GM1 预处理是否可能改变可卡因的药代动力学参数，评估了脑和血浆酯酶活性、血浆结合/游离可卡因比值以及脑血屏障对静脉注射 Evans Blue 的通透性。这些参数均未因 GM1 给药而改变。此外，GM1（100μM）不会改变可卡因（10-7-10-5M）诱导的多巴胺转运体抑制作用，这可以通过在伏隔核微囊中摄取 [(3-)H]-多巴胺来确定。总之，GM1 预处理本身没有任何作用，但增加了可卡因的奖赏效应，这一现象与大脑中可卡因水平的显著增加有关。评估的不同药代动力学参数，以及可卡因对多巴胺转运体的抑制作用，均不受 GM1 影响，但 GM1 会改变大脑中可卡因的分布。因此，GM1 增强可卡因奖赏效应的机制值得进一步研究。
