一氧化氮对间歇性主动饮酒大鼠戒断后再饮酒时酒精偏好的影响  

Effects of nitric oxide on alcohol preference in rats with intermittent active alcohol abstinence

作　　者：杨涛 高青 张洪艳[1] 王琦玉 王雪[1] 徐璐璐[1] 熊君伟 关艳中[1] YANG Tao(Mudanjiang Medical University, Mudanjiang 157011, China)

机构地区：[1]牡丹江医学院,黑龙江牡丹江157011

出　　处：《牡丹江医学院学报》2021年第4期5-7,15,共4页Journal of Mudanjiang Medical University

基　　金：国家自然科学基金面上项目(81871041,81371463);牡丹江医学院研究生创新科研项目(2019YJSCX-04MY)。

摘　　要：目的研究中脑腹侧被盖区(Ventral tegmental area,VTA)一氧化氮(Nitric oxid,NO)对大鼠饮酒行为的影响。方法雄性SD大鼠30只,随机分为对照组(n=6)和饮酒组(n=24)。对照组正常饮纯净水,饮酒组以间歇性主动饮酒模式饮用20%(v/v)酒精,21 d时对照组与饮酒组大鼠VTA进行脑立体定位埋置套管后,继续饮用水或20%酒精至28 d,监测体重及液体消耗量;建模成功后酒精戒断72 h,饮酒组大鼠随机分为假手术组[正常做手术但戒断72 h后VTA内不注射药物]、L-NAME组[VTA注射0.5μg/0.5μL Nω-硝基-L-精氨酸甲酯(Nω-Nitro-D-arginine methyl ester,L-NAME)]、C-PTIO组[VTA注射1μg/0.5μL 2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物钾盐(Carboxy-PTIO potassium salt,C-PTIO)]、生理盐水组(VTA微量注射0.5μL生理盐水),每组各6只,检测给药后6 h内的酒精偏好。结果饮酒组大鼠饮酒28 d后,酒精摄入量和饮酒偏好达到稳定基线;实验过程中对照组和饮酒组大鼠体重比较无显著差异(P>0.05)。VTA中微量注射L-NAME、C-PTIO后,与假手术组和生理盐水组相比,SD大鼠酒精偏好均明显降低(P<0.001)。结论大鼠间歇性主动饮酒28 d成功构建酒精依赖模型,L-NAME、C-PTIO均可以显著降低间歇性主动饮酒大鼠戒断后再次饮酒时的酒精偏好。Objective To study the effect of nitric oxide(NO)in the ventral tegmental area of midbrain on drinking behavior in rats.Methods Thirty male SD rats were randomly divided into the control group(n=6)and the alcohol group(n=24).The control group drank purified water normally,and the drinking group drank 20%(v/v)alcohol in an intermittent active drinking model.At 21 days,all rats were implanted with a cannula after brain stereotaxic localization of the VTA,and drinking water or 20%alcohol was continued until 28 days.During this time,body weight and fluid consumption were monitored.After 72 hours of alcohol withdrawal after successful modeling,alcohol group rats were randomly divided into sham operation group[normal surgery but no drug injection was performed],L-NAME group[Nω-nitro-L-arginine methyl ester],C-PTIO group[2-(4-carboxyphenyl)-4,5,5-tetramethylimidazoline-1-oxo-3-oxide potassium salt],and saline group.Alcohol preference was measured within 6 hours of administration.Results We successfully constructed the alcohol dependence model after drinking for 28 days as the alcohol intake and drinking preference reached a stable baseline.There was no significant difference in body weight between the control and alcohol consumption groups during the experiment(P>0.05).After microinjection of L-NAME and C-PTIO into the VTA,the alcohol preference of SD rats was significantly decreased,compared with the sham and vehicle group(P<0.001).Conclusion The alcohol dependence model was successfully established in rats with intermittent active drinking for 28 days,and L-NAME or C-PTIO could significantly reduce alcohol preference during re-drinking after withdrawal in intermittent active drinking rats.

关 键 词：酒精使用障碍 一氧化氮 酒精偏好 

分 类 号：R749.62[医药卫生—神经病学与精神病学]