吗啡依赖大鼠部分脑区前脑啡肽基因表达改变

目的 研究吗啡依赖大鼠部分脑区的前脑啡肽基因(PENK)转录水平的改变。方法 将24只雄性Sprague-Dawlay大鼠随机等分为吗啡组(iq·2次·d-1,剂量逐日递增,5-50mg·kg·次,共10d)及对照组(注射相同体积的生理盐水)。在末次注射后的3h及3d,每组各随机灌注处死6只,取脑组织并冰冻切片,留取含中脑腹侧被盖区(VTA)、伏隔核(NAC)、中脑导水管灰质(PAG)、杏仁核(AMG)、海马CAl区(HIPCAl)的切片。利用原位杂交技术及图像分析技术检测各脑区吸光度A值(PENKmRNA)的水平。结果末次注射后3h,吗啡组大鼠5个被检脑区PENK mRNA值,均显著低于同期对照组;末次注射后3d,在除AMG以外的4个被检脑区PENK mRNA值仍显著低于同期对照组。结论慢性吗啡处理可使多个脑区PENK基因表达明显下调,从而参与吗啡依赖与戒断。     

SD大鼠海洛因CPP易感性差异的伏隔核壳区D2受体及DAT机制

目的:建立大鼠海洛因成瘾易感性差异的条件性位置偏爱模型,检测海洛因CPP易感性差异大鼠伏隔核壳区(AcbSH)D2受体(dopamine D2 receptor,D2R)及多巴胺转运体(dopamine transportor,DAT)蛋白表达的动态变化,探讨海洛因精神依赖易感性差异可能机制.方法:130只雄性SD大鼠随机抽取30为生理盐水对照组(SC),其余100只大鼠为海洛因处理组进行条件性位置偏爱(CPP)训练,海洛因处理组根据海洛因诱导的CPP强度不同再分为高CPP组(HP)和低CPP组(LP),各占总数的30%,利用免疫组化方法对高、低偏爱组及生理盐水对照组大鼠末次海洛因注射后30分钟、戒断第1、3、7、14天AcbSH D2R和DAT蛋白表达进行检测.结果:①海洛因处理后大鼠AcbSH区D2R和DAT蛋白表达均显著下降,而在戒断后逐渐回升;②海洛因高偏爱组大鼠在所有检测时点AcbSH区D2R下凋比低偏爱组大鼠更为明显;③海洛因高偏爱组大鼠各脑区所有检测时点DAT表达与低偏爱组大鼠均无明显差别.结论:①海洛因慢性处理后,大鼠AcbSH区D2R和DAT均出现适应性下调;②不同个体D2R敏感性或受体水平存在差异,低D2R可能与海洛因成瘾的高易感性与有关;③未发现不同易感性的大鼠DAT蛋白水平存在差异,海洛因成瘾易感性与DAT的表达可能没有直接的相关性.     

丁丙诺啡舌下片合并东莨菪碱、异丙嗪药物依赖者停药后脑白质的弥散张量成像纵向研究

目的 观察中国南方新近出现的盐酸丁丙诺啡舌下片合并东莨菪碱、异丙嗪药物依赖者(BSP依赖者)停药后脑白质完整性的动态变化.方法 采用弥散张量成像(DTI)方法对16例BSP依赖者停药后第3天、第1个月以及第2个月各向异性分数(FA)进行了自身前后对比研究,并设立18例正常对照组.结果 与正常对照组相比,停药3dBSP依赖者额叶(14,48.- 16;28,-26,46)、胼胝体(18,30,-14;- 14,26,-12)、顶叶(-50,-26,26)、颞叶(-46,-40,6;34,- 62,8)区域白质FA值显著性低于正常对照组(P＜0.001).与停药3d相比,BSP依赖者停药1个月白质FA值没有变化,停药后2个月部分脑区白质FA值有所增高,包括左侧额上回(-20,50,18)、右侧额中回(30,- 20,44)以及右侧顶下小叶(38,-30,34),差异有显著性(P＜0.001).对比停药2个月BSP依赖者与正常对照组,先前受损严重的脑区额叶、胼胝体、顶叶、颞叶区域白质FA值仍低于正常对照组(P＜0.01).结论 BSP滥用导致白质完整性的损害随着戒断时间的延长,前额叶等受损脑区在停药2个月后可得到部分恢复,但仍不能达到正常水平.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

丁丙诺啡、东莨菪碱与异丙嗪联合使用对大鼠位置偏爱的影响

目的 通过观察丁丙诺啡、东莨菪碱与异丙嗪三药联合使用(俗称"1+1")对大鼠位置偏爱的影响,探索"1+1"对实验大鼠的精神依赖性潜力.方法 161只雄性SD大鼠随机分成9组,分别采用丁丙诺啡、丁丙诺啡+东莨菪碱、丁丙诺啡+异丙嗪、丁丙诺啡+东莨菪碱+异丙嗪、东莨菪碱、异丙嗪、东莨菪碱+异丙嗪、吗啡、以及生理盐水等进行腹腔内注射,同时进行药物匹配CPP训练,共10d,比较各组大鼠训练前后以及训练后各组大鼠之间在药物训练侧(简称伴药侧)停留时间的差异,探索各处理因素的精神依赖性潜力及其差异.结果 注射吗啡、丁丙诺啡、丁丙诺啡+东莨菪碱、丁丙诺啡+异丙嗪、丁丙诺啡+东莨菪碱+异丙嗪等5组大鼠均形成了明显的CPP;组间比较发现丁丙诺啡+东莨菪碱+异丙嗪组大鼠训练前后在非自然偏爱侧停留时间增加(378.6±120.8)s,明显高于丁丙诺啡组(302.2±133.9)s,差异有显著性(F=62.9,P=0.03),但与吗啡组(419.8±146.4)s比较,差异无显著性(F=14.3,P=0.63).结论 丁丙诺啡、东莨菪碱与异丙嗪之间可能存在协同作用而增加了丁丙诺啡的滥用潜力.     

虚拟现实治疗老年失眠共病焦虑的初步探索

目的：首次在共病焦虑的老年失眠障碍患者中探索虚拟现实（virtual reality,VR）干预的有效性和安全性。方法：纳入120名共病焦虑的老年失眠障碍患者，随机分入实验组与对照组。实验组在常规治疗基础上进行6天的VR干预，对照组仅接受常规治疗。干预前及干预结束后1日、1周、1月时对被试进行睡眠、情绪及安全性评估。结果：VR干预总体安全性良好；两组干预后的睡眠症状、焦虑抑郁水平较基线均显著降低（P<0.05）；尽管组间差异不显著（P>0.05），但在睡眠症状上，实验组在随访期显示出持续下降的趋势。结论：本研究初步证明了VR干预总体上的安全性及其存在长期获益的可能。研究结果为VR的临床应用提供了一定依据。     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

特麦角脲对大鼠海洛因自身给药的影响

目的 观察多巴胺D2受体部分激动剂--特麦角脲对大鼠海洛因固定比率、累进比率自身给药行为的影响.方法 对64只雄性SD大鼠分别处理如下:(1)取16只大鼠训练自身给水(自然奖赏模型对照),造模成功后随机分为2组,分别接受特麦角脲0.4 mg/kg和生理盐水腹腔注射干预,观察对大鼠固定比率自身给水行为的影响.(2)取32只大鼠训练海洛因固定比率自身给药,自身给药行为稳定后随机分为4组,每组8只,分别腹腔注射特麦角脲3种剂量(0.1,0.2,0.4 mg/kg体质量)和生理盐水(对照组),观察不同剂量特麦角脲对大鼠海洛因固定比率自身给药行为的影响.(3)取16只大鼠训练海洛因累进比率自身给药,造模成功后随机分为2组,分别接受特麦角脲0.4mg/kg和生理盐水腹腔注射干预,观察对大鼠海洛因累进比率自身给药行为的影响.结果 (1)特麦角脲0.4 mg/kg组固定比率自身给水行为与生理盐水干预组相比,差异无统计学意义(P>0.05).(2)特麦角脲0.2 mg/kg组和0.4 mg/kg组的大鼠海洛因固定比率自身给药次数干预前后的差值[(6.25±3.31)次和(11.75±4.92)次]高于生理盐水对照组[(-1.12±4.30)次],差异均有统计学意义(均P<0.01).(3)特麦角脲0.4 mg/kg组的大鼠累进比率自身给药的断点干预前后的差值[(20.2±8.7)次]高于生理盐水组[(-1.1±4.3)次],差异有统计学意义(P<0.01).结论 D2受体部分激动剂特麦角脲可降低海洛因固定比率和累进比率自身给药行为,以降低海洛因使用期的强化效应.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.     

大鼠伏隔核多巴胺D2受体及转运体与吗啡条件性位置偏爱易感性的关系

Objective To explore the possible role of the expression of dopamine D2 receptor (D2R)and dopamine transporter(DAT)located in the nucleur accumben(Nac)in rats with difierent CPP susceptibility.Methods Altogether 160 male Sprague-Dawley rats were randomly assigned into experiment group(n=130)and control group(n=30).The experiment rats were re-classified into three groups according to the numerical value of the CPP(conditioned place preference),high preference group(HP group,n=26),moderate preference group(n=78)and low preference group(LP group,n=26).At the time of 3 hours,72 hours and 14 days after the final injection,rats in each group were scarified,and the mRNA levels of D2R and DAT in Nac were estimated with in situ hybridization.Results No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P=0.470),however.the time stayed at the conditioned preference chamber during the test period minus the time stayed at pretest natural preference was significantly higher in the HP group than the LP group(P＜0.01).In each time-point,the expression of D2R mRNA in HP group,were lower that in LP group[(131±3,122±5,119±5)and(125±4,117±8,114±5),P＜0.01].In each time-point,the expression of DAT mRNA in HP group,were significantly lower than that in LP group[(161±5,143±4,134±6)and(156±5,139±3,130±4),P＜0.01].Conclusions It can be inferred that D2R and DAT may be correlated closely and underlie the difierent susceptibility to morphine induced CPP.