凉味剂对电子烟气溶胶吸入小鼠模型的成瘾性作用研究  

The Addiction-Like Behavioral Assessment of Cooling Agent in E-Vapor by A Long-Term Exposed Mouse Model

作　　者：徐智彬 齐旭刚 莫之准 汤佳航 吴泽宏 许静 姜兴涛 路中华 刘欣安 XU Zhibin;QI Xugang;MO Zhizhun;TANG Jiahang;WU Zehong;XU Jing;JIANG XingTao;LU Zhonghua;LIU Xinan(Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,CAS Key Laboratory of Brain Connectome and Manipulation,Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions,Brain Cognition and Brain Disease Institute(BCBDI),Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Guangdong,518055,China;University of the Chinese Academy of Sciences,Beijing,100049,China;RELX Lab,Shenzhen RELX Tech.Co,.Ltd.,Shenzhen,Guangdong,518101,China)

机构地区：[1]广东省脑连接图谱重点实验室,中国科学院脑联结解析与调控重点实验室,深港脑科学创新研究院,中国科学院深圳先进技术研究院脑认知与脑疾病研究所,广东深圳518055 [2]中国科学院大学,北京100049 [3]深圳雾芯科技有限公司科学中心,广东深圳518101

出　　处：《中国药物滥用防治杂志》2022年第4期413-419,457,共8页Chinese Journal of Drug Abuse Prevention and Treatment

基　　金：国家自然科学基金青年项目(编号:31900728)。

摘　　要：目的:本实验采用电子烟气溶胶慢性暴露小鼠模型,结合经典的奖赏性行为及戒断焦虑行为检测手段,研究电子烟雾化液及其凉味添加剂(WS-23)对成瘾行为的影响。方法:本实验分为溶剂组(PG/VG)、纯尼古丁组(PG/VG+尼古丁)、纯凉味剂组(PG/VG+WS-23)、凉味尼古丁组(PG/VG+WS-23+尼古丁)。实验小鼠在经过连续4周、每天半个小时的电子雾化液气溶胶全身雾化暴露后,采用条件位置性偏好实验以及情绪行为检测实验对各组雾化液气溶胶的奖赏性偏好和戒断症状进行评估。结果:(1)长期短时程周期气溶胶暴露并未引起小鼠明显的奖赏性偏好行为;纯凉味剂及凉味尼古丁气溶胶暴露导致小鼠产生明显的厌恶性行为。(2)停止暴露48小时后,凉味尼古丁气溶胶慢性暴露小鼠表现出一定程度的焦虑样行为;纯凉味剂及凉味尼古丁气溶胶暴露小鼠的运动减少;(3)纯尼古丁及凉味尼古丁气溶胶暴露小鼠戒断48小时后血清检测皮质酮水平都有升高趋势,提示含尼古丁气溶胶戒断后小鼠有焦虑相关的激素反应。结论:本研究通过建立电子烟气溶胶慢性暴露小鼠模型并结合奖赏相关行为学分析,鉴定了凉味剂本身不具有奖赏性,在与尼古丁雾化液混合后降低含尼古丁气溶胶对小鼠的奖赏性刺激。本研究中建立的技术方法将为电子雾化产品的成瘾性精神作用评估提供研究依据。Objective:To evaluate the addiction property of cooling flavor agent WS-23 in e-cigarette aerosols by using a mouse model with chronic exposure of e-cigarette aerosols and addiction-like behavioral assessments.Methods:Adult male C57BL/6J mice were randomly assigned to one of four treatment groups and exposed daily to the vapor of either propylene glycol and vegetable glycerol(50:50 PG/VG,vehicle);or to PG/VG with 4%(%vol/vol)nicotine(Nico);WS-23(5%)in PG/VG(WS-23);or 4%nicotine mixed with 5%WS-23 in PG/VG(WS-23+Nico).After four consecutive weeks,half an hour per day of systemic exposure,we utilized conditioned place preference test to evaluate the rewarding effect of the aerosols and anxiety-related test to investigate the withdrawal effect after cessation of exposure.Results:(1)Under our experimental condition,the exposure of PG/VG or PG/VG+nicotine aerosols did not induce conditioned place preference in mice.Interestingly,exposure of WS-23 or WS-23+nicotine aerosols induced conditioned place avoidance.(2)48-hours abstinence of exposure did not obviously increase anxiety level in mice with chronic WS-23 or WS-23+nicotine aerosol exposure.(3)48-hours abstinence of exposure trended to increase the level of stress hormone corticosterone in mice with exposure of nicotine or WS-23+nicotine aerosol.Conclusion:By establishing a chronic e-cigarette aerosol exposed mouse model and combined with addiction-related behavioral analyses,we have found that the cooling agent WS-23 itself is not rewarding and it can attenuate the rewarding effect of nicotine-containing aerosol in mice.The techniques and approaches established in this study will be useful for evaluating the addictive psychoactive effects of specific components of e-cigarette aerosols.

关 键 词：电子烟气溶胶 凉味剂 奖赏行为 戒断 焦虑 

分 类 号：R749.6[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]