内侧前额叶皮层参与可卡因诱导行为敏化的电生理机制研究

【作者】 刘晓东；

【导师】 袁逖飞；

【作者基本信息】 南京师范大学 ， 应用心理（专业学位）， 2018， 硕士

【摘要】 药物成瘾是危害社会安定的重要因素,可卡因是当前全球最为泛滥的毒品之一。药物成瘾的一项显著标志是行为敏化(behavior sensitization),即过度使用成瘾性药物可导致个体自发性活动显著增强,对冲动性觅药行为和毒品渴求均有重要影响。行为敏化受前额叶皮层(prefrontal cortex,PFC)、中脑腹侧被盖区(ventral tegmental area,VTA)和伏隔核(nucleus accumbens,NAc)等脑区调节,目前主要集中在对VTA和NAc的研究,而对PFC尤其是内侧前额叶皮层(medialprefrontal cortex,mPFC)关注较少。为了探究mPFC在可卡因诱导的行为敏化中的作用,本研究使用C57BL/6N小鼠分别从行为学水平上观察可卡因诱发其行为敏化以及mPFC锥体神经元放电活动的改变。研究结果表明:1.单次注射可卡因诱发小鼠在环形跑道中的自发性活动显著增强;长期(连续5天)注射可卡因引起小鼠的自发性活动呈现递增现象;长期注射可卡因戒断(停药10天)后再用可卡因诱导,小鼠的自发性活动进一步增强,表现出行为敏化的特征。2.在体细胞外电生理记录发现,单次注射可卡因引起小鼠mPFC锥体神经元电活动(自发放电和簇状放电频率)下降;长期注射可卡因(连续注射5天)和长期注射可卡因戒断后再用可卡因诱导后mPFC锥体神经元电活动均进一步下降。本研究结果提示:可卡因抑制mPFC锥体神经元电活动参与了可卡因成瘾的行为活动,为揭示药物成瘾的神经机制提供新观点,并为成瘾干预提供新思路。更多还原

【Abstract】 Drug addiction is an important factor endangering social stability.Cocaine is one of the most inundant drugs.The most prominent characteristic of drug addiction is behavioral sensitization,i.e.excessive use of addictive drugs evokes significant increase in spontaneous activity.And behavioral sensitization has been reported pertinent to impulsive drug seeking and addictive craving.It is believed that behavioral sensitization is mediated through the pathway of the ventral tegmental area(VTA),nucleus accumbens(NAc)and prefrontal cortex(PFC).However,current investigations are mostly focused on VTA and NAc,few studies are made on PFC,especially the medial PFC(mPFC).To explore the effect of mPFC in cocaine-induced behavioral sensitization,this study was delved into the change of cocaine-induced behavioral sensitization and the pyramidal neuron firing activities in mPFC based on ethology of C57BL/6N mice.The results were as follows:1.A single injection of cocaine significantly increases the mouse spontaneous activity in an annular track;and the mice demonstrate a progressive increment in the spontaneous activity during a period of successive 5-day injections;and the spontaneous activity show further enhancement at cocaine injection after a subsequent 10-day withdrawal,exhibiting a credible outcome of behavioral sensitization.2.Electrophysiological results show that acute cocaine evokes decrease of firing frequency(both the spontaneous firing and the burst firing)in the pyramidal neurons in mPFC.Both repeated cocaine injections(for successive 5 days)and 10-day withdrawal after repeated cocaine injections induce more remarkable decrease in neuronal firings.In conclusion,our present results indicate that cocaine-induced inhibition in mPFC neuronal activity is involved in addictive behaviors.These findings uncover a new mechanism underlying drug addiction and may provide new thoughts on addiction intervention.更多还原