Valdomero Analía, Perondi María C, Orsingher Otto A, Cuadra Gabriel R
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-IFEC (CONICET), Ciudad Universitaria, 5000 Córdoba, Argentina.
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba-IFEC (CONICET), Ciudad Universitaria, 5000 Córdoba, Argentina.
Behav Brain Res. 2015 Feb 1;278:303-6. doi: 10.1016/j.bbr.2014.10.013. Epub 2014 Oct 18.
Gangliosides are compounds that are abundant throughout the CNS, participating actively in neuroplasticity. We previously described that exogenous GM1 ganglioside pretreatment enhances the rewarding properties of cocaine, evidenced by a lower number of sessions and/or dosage necessary to induce conditioned place preference (CPP). Since GM1 pretreatment did not modify cocaine's pharmacokinetic parameters, we suspected that the increased rewarding effect found might be mediated by BDNF, a neurotrophic factor closely related to cocaine addiction. This study was performed to investigate the possibility that GM1 may induce changes in BDNF levels in the nucleus accumbens (NAc), a core structure in the brain's reward circuitry, of rats submitted to three conditioning sessions with cocaine (10 mg/kg, i.p.). The results demonstrate that GM1 administration, which showed no rewarding effect by itself in the CPP, induced a significant increase of BDNF protein levels in the NAc, which may account for the increased rewarding effect of cocaine shown in the CPP paradigm.
神经节苷脂是在整个中枢神经系统中含量丰富的化合物，积极参与神经可塑性。我们之前描述过，外源性GM1神经节苷脂预处理可增强可卡因的奖赏特性，这表现为诱导条件性位置偏爱（CPP）所需的训练次数和/或剂量减少。由于GM1预处理并未改变可卡因的药代动力学参数，我们推测所发现的奖赏效应增强可能是由脑源性神经营养因子（BDNF）介导的，BDNF是一种与可卡因成瘾密切相关的神经营养因子。本研究旨在探讨GM1是否可能诱导接受三次可卡因（10mg/kg，腹腔注射）条件训练的大鼠伏隔核（NAc，大脑奖赏回路的核心结构）中BDNF水平发生变化。结果表明，GM1给药本身在CPP中未显示奖赏效应，但却诱导了NAc中BDNF蛋白水平显著升高，这可能解释了CPP范式中可卡因奖赏效应增强的原因。
