青少年期尼古丁暴露对成年大鼠饮酒行为和腹侧被盖区nACh受体表达水平的影响  

EFFECTS OF NICOTINE EXPOSURE DURING ADOLESCENCE ON ETHANOL SELF-ADMINISTRATION IN ADULTHOOD AND nAChR EXPRESSION OF VTA ON RATS

作　　者：孟纲[1,2] 刘铁桥[1] 郝伟[1] 徐亚辉[1] 王珏璐[1] 廖艳辉[1] 王绪轶[1] WANG Jichuan 谌明卉[1] 张小洁[1] 

机构地区：[1]中南大学湘雅二医院精神卫生研究所,长沙410011 [2]广西医科大学第一附属医院心理卫生中心,南宁530007 [3]美国乔治华盛顿大学医学院,20010-2970

出　　处：《中国药物依赖性杂志》2011年第4期265-273,共9页Chinese Journal of Drug Dependence

基　　金：国家重点基础研究发展计划资助项目(2003C515400);湖南省自然科学基金项目(10JJ5038)

摘　　要：目的:观察大鼠青少年期尼古丁暴露对成年期大鼠饮酒行为的影响,检测青少年期尼古丁暴露和成年期大鼠饮酒行为对大鼠腹侧被盖区(VTA脑区)烟碱型尼古丁受体(nAChR)部分亚单位mRNA表达的影响。探讨VTA区nAChR受体参与青少年期吸烟和成年期酒依赖形成的可能机制。方法:39只Wistar大鼠出生后35 d(PN35)开始为期10 d的尼古丁(1.0 mg.kg-1/day salt)皮下注射(尼古丁处理组,N组n=20),以生理盐水作为对照处理(生理盐水对照组,C组n=19)。完成后各组随机抽取6只作为空白对照(E)组(分别为CE组n=6,NE组n=6),断头取脑分离VTA区提取mRNA,Real Time-PCR定量检测nAChR受体α4、α5、α7和β2亚单位mRNA。两组余下大鼠作为酒依赖模型(A)组(分别为NA组n=14,CA组n=12)于大鼠出生后60 d(PN60)以Samson糖水递减程序诱导建立乙醇双瓶自由选择饮酒行为实验,观测干预对Wistar大鼠乙醇消费量、酒偏好程度、总饮液量的影响。之后相同程序定量检测VTA标本相同指标。结果:青少年期尼古丁干预对成年期饮酒行为的各项行为学指标无明显影响(P>0.05)。VTA区nAChR亚单位mRNA的表达:未建立酒依赖模型两处理组间α4、α5、α7和β2亚单位mRNA表达无差异(P>0.05);建立酒依赖模型两处理组间α4、α5、α7和β2亚单位mRNA表达都有不同程度的显著性差异(P<0.05或P<0.001),其中尼古丁处理组α4、α5和β2表达上调,生理盐水处理组α7表达下调。因素分析显示:两因素对α4和α5亚单位表达都有调节作用;酒依赖模型因素对β2表达有调节作用;对α5、α7和β2亚单位表达两因素有交互作用。结论:(1)青少年期尼古丁干预可以调节VTA区nAChR亚单位α4、α5、α7、β2的表达,其效应在一定时间后才出现;没有发现青少年期尼古丁干预对成年期酒依赖形成行为学的促进作用,考虑可能有深层的内在原因相继造成了人类青少年期吸烟和此后酒依赖的形成。(2)VTAObjective：To observe the effects of nicotine exposure during adolescence on ethanol self- administration in adulthood and examine the effects on mRNA expression of some nAChR subunits in VTA;to explore the mechanisms of smoking during adolescence and alcoholism during adulthood. Methods：Wistar rats received a period of 10 day subcutaneous injections of nicotine（ 1.0 mg·kg^-1/day, salt） （N group n = 20）or of physiological saline （C group n = 19）on PN35. Six rats from each group （CE group n = 6, NE group n = 6） were randomly selected, and VTA were separated after killed. The total RNA were extracted, mRNA of α4, α5, α7 and β2 nAChR subunit in VTA of each group were measured by real time - PCR. Beginning on PN60, the left rats （ NA group n = 14, CA group n = 12） were induced to establish ethanol two -bottle free -choice self- administration by Samson sucrose fading program. Ethanol consumption, alcohol preference and total fluid intake were measured. Then the same target was measured by the same program. Results： There were no differences in ethanol consumption, alcohol preference and total fluid intake between nicotine and saline treatment during adolescence （P 〉 0.05 ）. The mRNA expressions of each nAChR subunit in VTA showed ： （ 1 ） There were no differences on mRNA expression of α4, α5, α7 and β2 nAChR subunit between two exposure groups （ P 〉 0.05 ）. （2） There were significant differences at different levels on mRNA expression of α4, α5, α7 and β2 nAChR subunits between two alcohol dependent model groups（ P 〈 0.05 or P 〈 0.001 ）. α4, α5, and β2 nAChR subunits were up - regulated and α7 nAChR subunit was down - regulated. Factorial ANOVA showed ： （ 1 ） mRNA expression of α4, α5 was modulated by both factors. （2） β2 was modulated by alcohol dependent model factor. （3）There were interactions between two factors on mRNA expression of α5, α7 and β2 nAChR subunits. Conclusion：（ 1 ）The mRNA expressions of α4, α5, α7

关 键 词：青少年期尼古丁暴露 酒依赖 烟碱型尼古受体 MRNA 

分 类 号：R599.9[医药卫生—内科学]