氯化锂通过Akt/GSK-3β通路抑制苯丙胺诱导的大鼠行为敏化  

Lithium chloride inhibits amphetamine-induced behavioral sensitization in rats via regulating the Akt/GSK-3βpathway

作　　者：白渊翰 曾志文 Bai Yuanhan;Zeng Zhiwen(Department of Bipolar Disorder,Shenzhen Mental Health Center,Shenzhen Kangning Hospital,Shenzhen 518118,China)

机构地区：[1]深圳市精神卫生中心,深圳市康宁医院双相障碍科,518118

出　　处：《神经疾病与精神卫生》2021年第4期238-242,共5页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金(81701315);广东省自然科学基金项目(2017A030313769);广东省高水平临床重点专科(深圳市配套建设经费)资助项目(SZGSP013);深圳市科创委项目(JCYJ20170306154944261);深圳市“医疗卫生三名工程”项目(SZSM201612006);深圳市医学重点学科建设经费资助项目(SZXK043)。

摘　　要：目的探讨氯化锂对苯丙胺诱导的大鼠行为敏化的影响及蛋白激酶B(Akt)/糖原合成激酶-3β(GSK-3β)通路在其中的作用。方法40只雄性SD大鼠随机分为空白对照组(S-S组,n=13)、苯丙胺敏化组(S-A组,n=13)和氯化锂预处理苯丙胺敏化组(L-A组,n=14),S-S组大鼠接受连续5 d的生理盐水(10 ml/kg)预处理+生理盐水(10 ml/kg)腹腔注射;S-A组大鼠接受连续5 d的生理盐水(10 ml/kg)预处理+苯丙胺(1.5 mg/kg)腹腔注射;L-A组大鼠接受5 d的氯化锂(100 mg/kg)预处理+苯丙胺(1.5 mg/kg)腹腔注射,之后停药6 d,第12天时每组随机选取6只大鼠接受低剂量苯丙胺腹腔注射。采用自发活动视频分析记录系统记录3组大鼠每组随机6只分别在用药第1天和第12天时150 min内的自发活动。第12天时在未接受行为学测试的3组大鼠中每组随机6只,采用Western blot检测其前额叶皮质磷酸化Akt(p-Akt)/Akt、磷酸化GSK-3β(p-GSK-3β)/GSK-3β表达水平。结果在用药第1天时,S-A组大鼠的自发活动总距离[(26826.50±5987.96)cm]明显高于S-S组[(1861.50±612.49)cm]和L-A组[(7599.00±4778.14)cm],差异均有统计学意义(均P<0.05)。在第12天时,苯丙胺激发实验中S-A组大鼠自发活动总运动距离[(43823.83±5831.88)cm]明显高于S-S组[(14274.50±4724.98)cm]和L-A组[(17823.50±4313.64)cm],差异均有统计学意义(均P<0.05)。S-A组大鼠前额叶皮质p-Akt/Akt比值和p-GSK-3β/GSK-3β比值均低于S-S组(均P<0.05),而L-A组大鼠前额叶皮质p-Akt/Akt比值和p-GSK-3β/GSK-3β比值高于S-A组(均P<0.05)。结论氯化锂可以抑制苯丙胺诱导的大鼠行为敏化,其机制可能是通过Akt/GSK-3β通路介导。Objective To investigate the effect of lithium chloride on amphetamine-induced behavioral sensitization in rats and the possible involvement of the Akt/GSK-3βpathway.Methods A total of 40 male SD rats were randomly divided into control group(S-S group,n=13),amphetamine group(S-A group,n=13)and lithium chloride and amphetamine group(L-A group,n=14).S-S rats were pretreated with normal saline(10 ml/kg)and intraperitoneally injected with normal saline(10 ml/kg)for 5 consecutive days.S-A rats were pretreated with normal saline(10 ml/kg)and intraperitoneally injected with amphetamine(1.5 mg/kg)for 5 consecutive days.L-A rats were pretreated with lithium chloride(100 mg/kg)and intraperitoneally injected with amphetamine(1.5 mg/kg)for 5 consecutive days.All injections came to a stop during the ensuing 6 days.On day 12,randomized 6 rats in each group were injected with a lower dosage of amphetamine.The spontaneous activityof three groups of rats was recorded by video recording system within 150 minutes on the 1st day and the 12th day of treatment,respectively.On day 12,6 rats that did not receive the behavioral test were selected from each group.Western blot was used to detect the expression of phosphorylated Akt(p-Akt)/Akt and phosphorylated GSK-3β(p-GSK-3β)/GSK-3βin prefrontal cortex.Results Compared to S-S[(1861.50±612.49)cm]and L-A[(7599.00±4778.14)cm]rats,a significant increase in spontaneous locomotor activity was observed in S-A rats[(26826.50±5987.96)cm]on the first day,and the differences were statistically significant(P<0.05).On day 12,S-A rats were associated with a significantly increased spontaneous locomotor activity[(43823.83±5831.88)cm]relative to S-S[(14274.50±4724.98)cm]and L-A[(17823.50±4313.64)cm]rats,and the differences were statistically significant(P<0.05).Ratios of p-Akt to Akt and p-GSK-3βto GSK3βshowed a significant decline in the prefrontal cortex of S-A rats compared to those in the prefrontal cortex of S-S(P<0.05)and L-A rats(P<0.05).Conclusions Lithium chloride can inhibit amphet

关 键 词：苯丙胺 行为敏化 锂盐 蛋白激酶B 糖原合成激酶-3β 

分 类 号：R965[医药卫生—药理学]