丹参对吗啡依赖大鼠戒断综合征的影响

目的研究丹参对大鼠吗啡戒断反应的影响。方法以剂量递增法形成吗啡依赖模型,用纳洛酮催促戒断,根据戒断评分和体质量丧失评定戒断症状的强度。结果 3种不同剂量(20、40、80mg/kg)的丹参对大鼠的吗啡戒断分值和体质量下降有明显抑制作用(P<0.05,P<0.01),并呈量效关系。结论丹参能抑制吗啡依赖大鼠的戒断症状。     

慢性吗啡处理及戒断对大鼠不同脑区突触素ImRNA表达水平的影响

目的 :探讨慢性吗啡处理及戒断对大鼠中脑腹侧被盖区 (VTA)、伏隔核 (NAc)、中脑导水管灰质 (PAG)、杏仁核 (AMG)、海马CA1区 (HIPCA1)突触素ⅠmRNA表达水平的影响。方法 :吗啡组大鼠ip吗啡 10d ,每日两次 ,剂量递增 ,对照组大鼠注射等量生理盐水。于末次注射后 3h及 72h处死 ,取脑并做冰冻切片。利用原位杂交技术检测各脑区突触素ⅠmRNA的水平并作同期比较。结果 :3h处死时 ,吗啡组大鼠突触素ⅠmRNA表达水平在VTA显著高于同期对照 (P <0 .0 1) ,在NAc、HIPCA1显著低于同期对照 (P <0 .0 5 )。自然戒断 72h时 ,吗啡组大鼠突触素ⅠmRNA表达水平在VTA仍显著高于同期对照 (P <0 .0 1) ,在AMG、HIPCA1显著低于同期对照(P <0 .0 5 )。结论 :吗啡慢性处理及戒断大鼠突触素ⅠmRNA表达在不同脑区有选择性的改变 ,可能是阿片依赖及戒断的分子机制之一     

慢性吗啡处理及戒断对大鼠不同脑区突触素ⅠmRNA表达水平的影响

目的 :探讨慢性吗啡处理及戒断对大鼠中脑腹侧被盖区 (VTA)、伏隔核 (NAc)、中脑导水管灰质 (PAG)、杏仁核 (AMG)、海马CA1区 (HIPCA1)突触素ⅠmRNA表达水平的影响。方法 :吗啡组大鼠ip吗啡 10d ,每日两次 ,剂量递增 ,对照组大鼠注射等量生理盐水。于末次注射后 3h及 72h处死 ,取脑并做冰冻切片。利用原位杂交技术检测各脑区突触素ⅠmRNA的水平并作同期比较。结果 :3h处死时 ,吗啡组大鼠突触素ⅠmRNA表达水平在VTA显著高于同期对照 (P <0 .0 1) ,在NAc、HIPCA1显著低于同期对照 (P <0 .0 5 )。自然戒断 72h时 ,吗啡组大鼠突触素ⅠmRNA表达水平在VTA仍显著高于同期对照 (P <0 .0 1) ,在AMG、HIPCA1显著低于同期对照(P <0 .0 5 )。结论 :吗啡慢性处理及戒断大鼠突触素ⅠmRNA表达在不同脑区有选择性的改变 ,可能是阿片依赖及戒断的分子机制之一     

达尔康对吗啡依赖大鼠戒断症状的影响

目的 :观察中药达尔康对吗啡依赖大鼠戒断症状的抑制作用。方法 :采用剂量递增法皮下注射吗啡 14d和3 0d ,分别建立大鼠吗啡依赖模型 ,观察达尔康大、中、小 3个剂量对吗啡依赖大鼠纳洛酮催促和自然戒断的戒断症状及体重的影响。结果 :达尔康能显著减轻吗啡依赖大鼠ip纳洛酮引起的催促戒断症状 (P <0 .0 5 )和体重下降(P <0 .0 1) ,能抑制自然戒断大鼠体重下降 (P <0 .0 1和P <0 .0 5 )。结论 :达尔康对吗啡依赖大鼠戒断反应有明显的抑制作用     

吗啡依赖及戒断大鼠相关脑区多巴胺D2受体基因表达的变化

目的:研究吗啡依赖及戒断大鼠相关脑区D2R基因表达的变化.方法:将24只雄性Sprague-Dawley大鼠随机等分为吗啡依赖组(吗啡组:在大鼠腹腔内注射盐酸吗啡,2次/d,起始剂量为5mg/kg,逐日递增5 mg,至第10天为50 mg/kg)及生理盐水对照组(对照组:用相同方式注射同体积的生理盐水),于末次注射后3 h及72 h处死(每组每时间点各6只),取中脑腹侧被盖区(VTA)、伏隔核(Nac)、中脑导水管灰质(PAG)、尾壳核(CPU)、海马CA1区(HIPCA1)等脑组织.利用组织原位杂交技术检测各脑区的D2R mRNA的吸光度(A)值,并作同期平行比较.结果:末次注射3 h,吗啡组大鼠五个被检脑区D2R mRNA A值均低于同期对照;末次注射72 h,尾壳核高于同期对照,其它四个被检脑区仍低于同期对照,差异具有显著性(P<0.05或0.01).结论:慢性吗啡处理可抑制大鼠相关脑区D2R基因表达,戒断后有不同程度的恢复.     

CCK-8对吗啡成瘾大鼠戒断症状及尾核内c-jun蛋白表达的影响

目的从行为学、形态学角度,初步研究了八肽胆囊收缩素(CCK-8)对吗啡成瘾大鼠戒断症状及尾核(Cd)内原癌基因c-jun蛋白表达的影响。方法采用动物行为学评估和免疫组化的方法,观察吗啡成瘾大鼠Cd内注入CCK-8(10mg.L-1,1μl)对c-jun蛋白表达和戒断症状的影响。结果①吗啡成瘾组大鼠戒断症状与生理盐水对照组大鼠行为学相比有差异;②吗啡成瘾大鼠在戒断24h时,Cd内注入CCK-8可使戒断症状降低,在戒断40h时戒断症状总分最明显;③单纯吗啡成瘾组大鼠Cd内c-jun蛋白表达与生理盐水对照组大鼠相比下降,而注入CCK-8后c-jun蛋白的表达上升。结论①成功建立吗啡成瘾大鼠模型;②Cd内注入CCK-8可使吗啡成瘾大鼠的戒断症状明显减少;③Cd内注射CCK-8可提高c-jun蛋白的表达。提示CCK-8能调控吗啡成瘾大鼠戒断症状的产生及Cd内c-jun蛋白的表达。     

吗啡依赖大鼠和小鼠戒断后应激行为和激素水平的观察

本文观察了吗啡依赖大鼠和小鼠的纳络酮催促后的行为学表现为其血中三咱激素水平的变化。结果显示，吗啡依赖性大鼠和小鼠的戒断症状与机体在应激状态下的表现极为相似，其应激能力明显高于对照组，戒断反应发生后其血清皮质酮、血管紧张素Ⅱ和胰高血糖水平亦明显高于对照组，本文认为，戒断症状的产生可能与阿片类对中枢的长期作用使机体产生了一种反适应性的应激反应有关。     

吗啡依赖及戒断大鼠糖皮质激素及其受体mRNA表达水平的改变

目的:研究慢性吗啡处理和吗啡戒断对大鼠血清中ACTH及其受体mRNA表达水平的影响。方法:利用放射免疫法测定吗啡依赖及戒断大鼠血清中ACTH及皮质醇的浓度;利用核酸分子杂交技术研究下丘脑糖皮质激素受体(GR)基因表达的改变情况。结果:(1)吗啡依赖组大鼠血清中ACTH及皮质醇的浓度明显低于对照组;戒断d1大鼠血清ACTH浓度仍明显低于对照组(P<0.01),但血清皮质醇的浓度则明显高于对照组(P<0.01);戒断d7大鼠血清ACTH浓度与对照组比较,无显著性差异(P>0.05),而血清皮质醇的浓度仍略高于对照组(P<0.05);(2)吗啡依赖组大鼠下丘脑GR基因表达水平下降(P<0.05),戒断组大鼠GR的基因表达均高于对照组,但无显著性差异(P>0.05)。结论:吗啡类物质的长期使用可以对下丘脑-垂体-肾上腺轴的激素分泌功能及GR的基因表达产生明显的抑制作用。     

川芎嗪对吗啡依赖大鼠戒断综合征的抑制作用

目的··:观察川芎嗪对吗啡依赖大鼠戒断综合征的影响。方法··:采用剂量递增方式皮下注射吗啡5d的大鼠,经过川芎嗪处理30min后,用纳洛酮催促,在停用吗啡后不同时间里观察评定戒断症状分值。结果··:川芎嗪明显减轻戒断症状和体重下降。结论··:川芎嗪能明显抑制吗啡依赖大鼠的戒断反应,其作用机制可能与阻断细胞钙内流有关。     

卡马西平对吗啡依赖大鼠戒断症状及ACTH的影响

目的 :观察卡马西平 (Carb)对吗啡依赖大鼠纳洛酮催促戒断症状的抑制作用及血清促肾上腺皮质激素(ACTH)水平的影响。方法 :剂量递增法皮下注射 (sc)盐酸吗啡 (Mor) ,建立大鼠吗啡依赖模型 ,腹腔注射 (ip)盐酸纳洛酮 1mg·kg- 1 催促 ,观察戒断反应并评分 ;免疫发光法测定血清ACTH水平。结果 :Carb 10 0mg·kg- 1 及 2 0 0mg·kg- 1 均可明显减轻大鼠戒断症状 (P <0 0 5 )。 10 0mg·kg- 1 剂量组的ACTH水平接近正常 ,低于Carb 2 0 0mg·kg- 1 组(P <0 0 5 )。结论 :适当剂量的卡马西平可有效控制吗啡依赖大鼠的戒断症状     

Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain

AIM: To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS) had been established. RESULTS: The chronic morphine administration (ip) resulted in a marked decrease in the brain concentrations of pregnenolone (PREG), progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after the last treatment. In contrast, there were no significant effects of morphine dependence on the brain concentrations of allopregnanolone (AP), dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS). Naloxone-induced withdrawal produced a significant increase in the concentrations of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group. CONCLUSION: Morphine dependence and withdrawal affected the concentrations of neurosteroids in rat brain, which suggests that endogenous neurosteroids in brain might be     

吗啡依赖及戒断大鼠脊髓和脑干中一氧化氮合酶基因的表达

目的　观察吗啡依赖或吗啡戒断大鼠脊髓和脑干中一氧化氮合酶 (NOS)基因表达的变化。方法　以 β actin为内参照 ,用逆转录聚合酶链反应 (RT PCR)测定NOSmRNA的表达水平。结果　吗啡依赖大鼠脊髓和脑干NOS表达水平较正常对照大鼠降低 ,纳洛酮 ( 4mg·kg-1,ip)激发大鼠吗啡戒断症状 1h后脊髓和脑干中NOS表达水平明显升高 ,戒断 2h和 4h后NOS基因表达较 1h组减少。NOS抑制剂L N 硝基精氨酸甲酯 (L NAME ,10mg·kg-1)处理后大鼠吗啡戒断症状减少 ,同时脊髓和脑干的NOS基因表达水平较戒断 1h组明显降低。甲基东莨菪碱 ( 0 5mg·kg-1)处理组脊髓和脑干中NOS表达水平较戒断 1h组明显降低 ;选择性毒蕈碱受体M1拮抗剂 pirenzepine( 10mg·kg-1)处理组动物脊髓中NOS表达水平较戒断 1h组降低 ,而脑干中NOS表达水平没有改变 ;NMDA受体拮抗剂MK 80 1( 0 12 5mg·kg-1)处理后脊髓和脑干中NOS表达水平较戒断 1h组没有差异。结论　吗啡慢性处理后脊髓和脑干中NOSmR NA水平降低 ,抑制内源性NO生成和阻断毒蕈碱受体可以减少吗啡戒断所引起脊髓和脑干中NOS基因的表达     

吗啡依赖对大鼠不同脑区内神经甾体水平的影响

目的建立大鼠条件性位置偏爱(CPP)模型，探讨吗啡精神依赖对大鼠脑内神经甾体水平的影响。方法 大鼠连续10 d腹腔注射吗啡5 mg·kg^-1，诱导CPP形成。高效液相色谱-质谱法测定大鼠伏隔核、杏仁核、下丘脑和血浆中脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯及孕烯醇酮硫酸酯的含量。结果经10 d吗啡训练后，吗啡组大鼠在伴药侧的停留时间显著长于对照组，吗啡诱导的大鼠CPP形成。与对照组相比，吗啡组大鼠下丘脑内孕烯醇酮明显降低，伏隔核和血浆中的脱氢表雄酮明显降低。结论吗啡诱导CPP形成，吗啡处理影响大鼠脑内某些神经甾体的水平，表明内源性神经甾体可能参与吗啡依赖的形成。     

慢性吗啡处理对大鼠交感神经节pCREB和CREB mRNA表达的影响

目的观察慢性吗啡(Mor)处理对大鼠交感神经节-颈上神经节(SCG)环腺苷酸反应元件结合蛋白(cAMP responseelement binding protein,CREB)磷酸化和mRNA表达的影响。方法 Wistar大鼠随机分成4组(正常对照组、吗啡急性给药组、吗啡依赖组、吗啡戒断组),免疫组织化学方法及RT-PCR法分别检测磷酸化的CREB(phosphorylated CREB,pCREB)和CREB mRNA在SCG中的表达。结果 (1)与正常对照组相比,吗啡急性给药组大鼠SCG中pCREB含量明显降低(P<0.05);(2)吗啡依赖组大鼠SCG中pCREB含量回到正常对照组水平,并有增高趋势(与正常对照组比较,P>0.05;与吗啡急性给药组比较,P<0.01);(3)吗啡戒断组大鼠SCG中pCREB含量明显高于正常对照组(P<0.01);(4)各组大鼠SCG的CREBmRNA表达无差异(P>0.05)。结论慢性吗啡处理大鼠交感神经节CREB磷酸化水平存在适应性上调现象。     

Effects of haloperidol on morphine-induced antinociception morphine tolerance and withdrawal in hyperprolactinaemic rats

Male rats with hyperprolactinaemia, induced by adenohypophyseal homografts under the kidney capsule, were injected with haloperidol for 3 days and then subjected to treatment with morphine, administered twice in a day at increasing doses for 12 days. At the first treatment, morphine induced an antinociceptive effect that was more prolonged in homografted rats than in sham-operated controls. The pretreatment with haloperidol did not change the prolongation of morphine-induced antinociception in homografted rats. After 12 days of treatment with morphine, all animals were tested for the development of tolerance to the antinociceptive effect of morphine. Pituitary homografts resulted in an inhibition of the development of tolerance, while this effect was absent in homografted rats pretreated with haloperidol. At the end of the treatment with morphine, the naloxone-precipitated abstinence syndrome was studied. Homografted rats shown an attenuation of the withdrawal syndrome and pretreatment with haloperidol did not change this response.These results suggest an involvement of dopaminergic transmission in prolactin-induced changes in the development of tolerance to morphine, but not in the antinociceptive effect following an acute injection of morphine and in naloxone-precipitated withdrawal syndrome of the rat.     

Repeated central administration of selegiline attenuated morphine physical dependence in rat

BackgroundLong-term exposure to opiates induces physical dependence; however, the neurobiological mechanisms of this phenomenon are not completely clear. The purpose of this study was to evaluate the effects of systemic and intracerebroventricular (icv) administration of selegiline (a selective inhibitor of monoamine oxidase B) on the morphine withdrawal syndrome in rats.MethodsTo this aim, adult male Sprague Dawley rats were selected randomly, and then growing doses of morphine were administered subcutaneously at an interval of 12 h for nine days with the intention of inducing dependency. Nine days after, only the morning dose of morphine was administered, followed by systemic or central injection of saline or selegiline. Later, naloxone was injected after 30 min and withdrawal signs recorded for a period of 60 min.ResultsResults showed failure of systemic administration of selegiline in changing the withdrawal symptoms; nevertheless, icv injection attenuated the withdrawal signs significantly.ConclusionIn conclusion we found that central administration of selegiline attenuated morphine withdrawal symptoms     

吗啡依赖和复吸时大鼠脑内神经甾体水平的变化

目的探讨吗啡精神依赖和复吸对大鼠脑内神经甾体水平的影响。方法采用条件性位置偏爱(CPP)实验,吗啡诱导大鼠CPP形成,足底电击应激诱发CPP重建,高效液相色谱-质谱法测定大鼠额叶皮质、海马及血浆中孕烯醇酮(PREG)及其硫酸酯(PREGS)、别孕烯醇酮(AP)、脱氢表雄酮(DHEA)及其硫酸酯(DHEAS)的含量。结果5 mg.kg-1吗啡训练10 d诱导大鼠产生了稳定的CPP,间歇足底电击有效诱发CPP的重建。与对照组比较,吗啡CPP形成时,大鼠额叶皮质内DHEA、PREG水平升高(P<0.05),海马内DHEA水平降低(P<0.05);与吗啡消退组比较,足底电击诱发CPP重现时,大鼠额叶皮质内PREG水平降低(P<0.01),而海马内PREG水平升高(P<0.05)。结论大鼠额叶皮质和海马内神经甾体水平的变化可能与吗啡依赖和复吸有关。     

大鼠损毁蓝斑和利血平处理对阿片类药物身体依赖性的影响(英文)

目的:探讨蓝斑去甲肾上腺素能(LC-NA)神经元在阿片类药物依赖中的作用.方法:用6-羟基多巴胺4 g·L~(-1)和利血平(Res)造成蓝斑损毁和中枢NA耗竭.慢性用吗啡(Mor)或二氢埃托啡(DHE)后,ip纳洛酮4 mg·kg~(-1)催促戒断,对戒断症状综合评分并记录体重丧失.结果:损毁蓝斑加重Mor用药鼠戒断症状,但不明显影响DHE用药鼠戒断症状.多剂量Res(0.5 mg·kg~(-1)·d~(-1)×3d)升高Mor和DHE用药鼠戒断症状记分;加重Mor而非DHE用药鼠体重丧失.单剂量Res 0.5 mg·kg~(-1)加速Mor身体依赖的形成.结论:LC-NA神经元对抑制某些阿片类戒断症状起作用.     

Development of morphine tolerance and physical dependence in rats depleted of brain catecholamines by 6-hydroxydopamine

The present study was undertaken to evaluate the roles of brain norepinephrine (NE) and/or dopamine (DA) in the development of morphine tolerance and physical dependence in rats. Rats were permanently depleted of brain catecholamines (CA, i.e. NE + DA) or DA by 6-hydroxydopamine (6-OHDA) treatment alone or desmethylimipramine plus 6-OHDA treatment at two weeks of age. Five weeks after either treatment, twice daily morphine injections were begun and continued for 32 consecutive days. The antinociceptive activity of morphine in the tail-flick test and the naloxone-precipitated abstinence syndrome were periodically observed throughout the course of chronic morphine treatment. A decreased antinociceptive response to morphine occurred in DA-depleted rats in both the non-tolerant and tolerant states, but the development of tolerance was not affected. The antinociceptive effect of morphine was not modified in either non-tolerant or tolerant CA (NE + DA)-depleted rats, nor was the development of tolerance affected. The spontaneous withdrawal syndrome after abrupt cessation of morphine after 32 days of treatment was markedly enhanced in CA-depleted rats. The results suggest that DA may be involved in mediating the antinociceptive effect of morphine, but not in the development of tolerance to that effect.     

慢性吗啡处理对大鼠交感神经节cAMP、cGMP水平的影响

目的观察慢性吗啡(Mor)处理对大鼠交感神经节——颈上神经节(SCG)环腺苷酸(cAMP)和环鸟苷酸(cGMP)含量的影响。方法剂量递增法连续皮下注射(sc)吗啡5 d建立慢性吗啡依赖大鼠模型,纳洛酮(Nal)催促戒断法和55℃热水甩尾试验判断模型依赖性和耐受性,125I放射性免疫测定法测定SCG中cAMP和cGMP的含量。结果①吗啡急性给药组大鼠SCG中cAMP含量较正常对照组降低(P<0.05);②吗啡依赖组大鼠SCG中cAMP含量回到正常对照组水平,并有增高趋势(与正常对照组比较,P>0.05;与吗啡急性给药组比较,P<0.05);③吗啡戒断组大鼠SCG中cAMP含量较正常对照明显增高(P<0.05);④各组大鼠SCG的cGMP含量差异无显著性(P>0.05)。结论慢性吗啡处理大鼠交感神经节cAMP存在适应性上调现象。