迷走神经刺激结合电针对条件线索诱导觅药行为的干预作用及其分子生物学机制  

Effects of Vagus Nerve Stimulation Plus Electro-Acupuncture on Drug-seeking Induced by Condition Cues and Its Molecular Biology Mechanisms

作　　者：刘宜军[1] 周文华[2] 张富强[2] 刘惠芬[2] 陈为升[2] 杨国栋[2] 

机构地区：[1]上海中医药大学基础医学院,上海201203 [2]宁波市微循环与莨菪类药研究所,浙江宁波315010

出　　处：《河南中医》2008年第11期38-41,共4页Henan Traditional Chinese Medicine

基　　金：国家重大基础研究项目(编号:CB2003515404);国家自然科学基金课题(编号:30670675)

摘　　要：目的:观察迷走神经刺激(vagus nerve stimulation,VNS)结合电针疗法对条件性线索诱导的大鼠海洛因觅药行为的影响,揭示其作用的分子生物学机制,为临床抗复吸提供实验依据。方法:应用固定比率程序(fixed ratio,FR)1建立大鼠海洛因自身给药模型,随机分为3组:电针(electroacqupuncture)组、VNS组及VNS结合电针组,每组6只。处理30min,每天1次,连续10d。用条件性线索诱导海洛因觅药行为,观察上述方法对条件性线索诱导的觅药行为的影响。用Western blotting方法检测各组伏隔核(NAc)、前额皮层(PFC)等相关脑区△FosB蛋白表达。结果:迷走神经弱刺激结合电针处理后使条件线索诱导的有效鼻触数比电针组及VNS组显著减少(P=0.019,P=0.006)。迷走神经激结合电针处理后大鼠自由活动度较VNS组显著增多(P=0.032)。迷走神经刺激结合低频弱电针组大鼠NAc中△fosB表达较电针组和VNS组均显著减少(P=0.000,P=0.001)。该组CPU中△fosB的表达较电针组显著减少(P=0.001)。该组NTS中的表达较与电针组和VNS组均显著增加(P=0.000,0.000)。结合组的PFC、BST中△fosB表达较电针组显著增多(P=0.000,0.016)。结论:电针结合迷走神经刺激可减少大鼠的觅药行为,增加其活动度。作用的机制部分可能是通过调节一些脑区△FosB蛋白表达以激活上行通路强化前额皮层功能,从而削弱VTA-NAc奖赏通路的长时程适应。Objective：The study was perofrmed to investigate the of vagus nerver stimulation plus electro-acupuncture on drug-seeking induced by cues and the possible molecular biology mechanisms underlying it by oberseving the expression of transcriptional protein molecule and provide expexperimental proof for anti-relapse in clinic.Methods：The rats were trained to acquire heroin self-administration（SA） under fixed ratio reinforcement schedule 1（FR1）.After dayily 4-h self-adminisrration training session for 10 consecutive days,rats acquired herion self-administration were divided into 3 groups;vagus nerve stimu lation group,electro-acupuncture（EA） group and VNS plus EA group.There are 6 rats in each group.They were treated once a day for 10 days.Then rats were put into the previously trainning cages with environmental stimuli to extinct the drug seeking behavior.The active pokes were recorded.After the last treatment and extinct trainning,the rats＇drug seeking behavior.The active pokes were recorded.After the last treatment and extinct trainning.the rats＇ drug seeking induced by the conditioned cues were recorded.Western blotting was applied to detect the expression of DFos B protein in related brain region,Result：Compared with EA and VNS group,the active pokes was significantly reduced（P=0.019,P=0.006）,ΔFos B in NAc was decreased notably in VNS plus low frequency EA group compared with the electro-acupuncture（EA） or VNS group（P =0.000,P=0.001）,ΔFosB in CPU in the treatment group was significantly reduced compared with EA group,The locomotor activity of VNS＋EA group was significantly higher than than of VNS group,ΔFosB expresion in NTS in the treatment group compared with EA or VNS group（P=0.000,0.000）.the expression of ΔFosB in PFC and BST in treatment group were increased markably compared with that of EA group.Conclusions：VNS plus electro-acqupuncture could the reduce the heroin drug seeking and reinforce the activity of rat .3.The molecular mechanism underlying it may be

关 键 词：迷走神经刺激 电针 复吸 ΔFosB 

分 类 号：R245.91[医药卫生—针灸推拿学]