单次注射人工合成大麻素降低大鼠中脑腹侧背盖区多巴胺能神经元兴奋性

摘要

大麻成瘾可能维持一生.中脑腹侧背盖区(ventral tegmental area,VTA)作为投射到意识及情绪相关皮层和边缘系统的多巴胺能神经元的主要来源,是奖赏系统的关键部位之一,与药物成瘾密切相关.目前,对于VTA多巴胺能神经元在药物成瘾过程中的作用研究,主要集中在药物成瘾过程中突触可塑性的变化.已有研究表明,大麻素慢性作用5天后,易化了低频电刺激诱导VTA多巴胺能神经元产生突触传递的长时程减弱(long-term depression,LTD)效应,而此过程中多巴胺能神经元兴奋性的变化情况还未见报道.实验中,作者采用离体脑片膜片钳技术,观察单次注射人工合成大麻素HU210对大鼠VTA区多巴胺能神经元兴奋性的影响.结果显示,HU210作用后,神经元基强度增大,平均放电频率降低,其细胞膜电生理特性也发生了改变,表明单次注射人工合成大麻素HU210,降低了VTA多巴胺能神经元的兴奋性,提示神经元内在兴奋性的可塑性改变可能在药物成瘾中发挥作用.%Cannabinoids can cause a lifetime addiction effect. As the main source of dopaminergic neurons projecting to the cortex and the limbic system related to consciousness and emotions, the ventral tegmental area (VTA) is one of the key parts of reward system and closely related to drug addiction. Previous studies of the role that VTA dopaminergic neurons play in drug addiction focused on synaptic plasticity, while much less attention has been given to the changes of intrinsic excitability of neurons. In the present study, the whole cell patch clamp technique was used to explore the changes of excitability of VTA dopaminergic neurons following single cannabinoid (HU210) exposure. The results showed that resting membrane potential decreased, rheobase increased and mean firing frequency decreased in VTA dopaminergic neurons from HU210-treated animals. The results indicated that single HU210 exposure decreases the intrinsic excitability in VTA dopaminergic neurons.