中脑腹侧被盖区MAPK在脑源性神经营养因子调节酒精偏好行为中的作用机制  

The mechanism of MAPK involved in alcohol preference behavior regulated by BDNF in the ventral tegmental area

作　　者：王家晞 熊君伟 武晓彬 王鹏宇[1] 王佳佳 关艳中[1] WANG Jia-xi(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》2023年第4期17-20,共4页Journal of Mudanjiang Medical University

基　　金：国家自然科学基金(81871041);黑龙江省自然科学基金重点项目(ZD2022H007)。

摘　　要：目的研究腹侧被盖区(ventral tegmental area,VTA)中丝裂原活化蛋白激酶(mitogen-activiated protein kinase,MAPK)参与脑源性神经营养因子(Brain-drived neurotrophic factor,BDNF)调节酒精偏好的作用机制。方法SD大鼠随机分为饮水组(n=6只)和饮酒组(n=36只),采用间歇性主动饮酒(Intermittent access two-bottle choice,IA2BC)范式建立酒精依赖模型,饮水组双瓶自由选择饮水,饮酒组在第21天进行脑立体定位手术,并在VTA内植入套管。饮酒组在术后创伤恢复期继续饮酒至第28日;待饮酒组酒精摄入量达到稳定水平后开始酒精戒断72 h,再将其随机分为Sham组、PBS组、U0126(MAPK抑制剂)组、C16-PAF(MAPK激活剂)组,BDNF组和BDNF+U0126组。每组分别在VTA注射相应的药物,30 min后分别测量大鼠水和酒精的摄入量。结果饮酒组和饮水组大鼠体重以及24 h总液体摄入量无统计学差异(P>0.05),饮酒组在第28日酒精摄入量达到(42.01±4.35)mL/24 h,且饮酒偏好达到(39.51±2.52)%;与Sham组和PBS组比较,BDNF组大鼠酒精偏好显著降低(P<0.001);U0126组大鼠酒净偏好无显著变化(P>0.05);C16-PAF组酒精偏好降低(P<0.001);值得注意的是,VTA BDNF和U0126联合注射会增加大鼠酒精偏好,即U0126拮抗BDNF对大鼠酒精偏好的调节作用(P<0.01)。结论VTA TrkB-MAPK可能参与BDNF调控大鼠酒精偏好行为,可为酒精依赖中枢调控机制增加新资料并提供可靠依据。Objective To study the mechanism of mitogen-activiated protein kinase(MAPK)in participating in alcohol preference mediated by which Brain-drived neurotrophic factor(BDNF)in VTA.Methods SD rats were randomly divided into drinking water group(n=6)and drinking group(n=36).Alcohol dependence model was established by using intermittent access two-bottle choice(IA2BC).In the drinking water group,two bottles of water were freely selected.In the drinking group,stereotaxic surgery was performed on day 21 and cannula was implanted in the VTA.The drinking group continued to drink alcohol until the 28th day during the postoperative trauma recovery period.After alcohol intake in the drinking group reached a stable level,rats began to abstain for 72h and then were randomly divided into Sham group,PBS group,U0126(MAPK inhibitor)group,C16-PAF(MAPK activator)group,BDNF group and BDNF+U0126 group.Each group was injected with the corresponding drug in the VTA,and the intake of water and alcohol were measured 30 minutes later,respectively.Results There was no significant difference in body weight and 24h total fluid intake between the drinking water group and the drinking group(P>0.05).The alcohol intake of the drinking group reached 42±4.35 mL/24h on the 28th day,and the drinking preference reached(39.5±2.5)%.Compared with Sham group and PBS group,alcohol preference of rats in BDNF group was significantly decreased(P<0.001).There was no significant change in net alcohol preference in U0126 group(P>0.05).Alcohol preference decreased in C16-PAF group(P<0.001).It was worth noting that the combined injection of VTA BDNF and U0126 increased the alcohol preference of rats,that was,U0126 antagonized the regulatory effect of BDNF on alcohol preference of rats(P<0.01).Conclusion VTA TrkB-MAPK may be involved in the regulation of alcohol preference in rats by BDNF,which may add new data and provide a reliable basis for the central regulatory mechanism of alcohol dependence.

关 键 词：AUD MAPK 酒精偏好 

分 类 号：R749.62[医药卫生—神经病学与精神病学]