噻诺啡灌胃对小鼠吗啡行为敏化的影响

目的研究ig噻诺啡对小鼠吗啡行为敏化的影响。方法测定小鼠的自主活动，观察ig噻诺啡对小鼠自主活动及急性给予吗啡所诱导小鼠活动增强效应的影响；建立小鼠吗啡行为敏化模型，观察ig噻诺啡对行为敏化形成、转化及表达的影响。结果单次ig噻诺啡(1.25-5.0 mg·kg^-1)可剂量依赖性地降低小鼠的自主活动(P<0.01)，但多次给药可产生耐受。噻诺啡可有效地抑制急性给予吗啡所诱导的小鼠高活动性(P<0.05)及小鼠吗啡行为敏化的形成、转化和表达(P<0.05或P<0.01)。结论噻诺啡可抑制小鼠中枢神经系统，对阿片类药物的滥用和成瘾可能具有干预作用。     

槟榔碱对小鼠吗啡行为敏化的影响

目的:探讨槟榔嚼块的主要成分—槟榔碱,对小鼠吗啡行为敏化过程的影响。方法:测定小鼠的自主活动,观察ip槟榔碱对小鼠的自主活动及单次给予吗啡所诱导的小鼠高活动性的影响;建立吗啡诱导的小鼠行为敏化模型,观察槟榔碱对行为敏化形成、表达的影响。结果:(1)单次ip槟榔碱(0·25-2·0mg·kg-1)可剂量依赖性地抑制小鼠的自主活动(P<0·05),多次给药后这种抑制作用既不产生耐受,也不形成敏化;(2)槟榔碱(2·0mg·kg-1)可增强单次给予吗啡所诱导的小鼠的高活动性(P<0·05);(3)槟榔碱(2·0mg·kg-1)可增强吗啡诱导小鼠行为敏化的形成(P<0·05);(4)虽然槟榔碱(2·0mg·kg-1)多次给药降低吗啡诱导小鼠行为敏化表达的程度(P<0·05),但是槟榔碱(0·5-2·0mg·kg-1)单次给药不影响吗啡诱导小鼠行为敏化的表达。结论:槟榔嚼块中的主要成分槟榔碱能增强小鼠吗啡诱导的急性高活动性和吗啡行为敏化的形成,提示槟榔嚼块有可能增强吗啡的成瘾性。     

大麻二酚对甲基苯丙胺诱导小鼠行为敏化及条件性位置偏爱的影响

目的 研究大麻二酚(CBD)在甲基苯丙胺(METH)成瘾中的对抗作用。方法 以雄性C57BL/6J小鼠为研究对象，采用小鼠行为敏化实验，分别观察形成期伴随ip给予或激发期单次ip给予CBD 20,40和80 mg·kg^-1后小鼠运动距离，评价CBD对行为敏化形成或点燃的影响；采用小鼠条件性位置偏爱(CPP)实验，分别观察形成期伴随ip给予、表达期测试前单次ip给予或消退期伴随多次ip给予CBD 20,40和80 mg·kg^-1后小鼠CPP得分，评价CBD对CPP形成、表达和重建的影响。结果 在行为敏化实验中，CBD 40和80 mg·kg^-1显著抑制METH诱导行为敏化的形成或点燃(P<0.05)。CPP实验中，CBD各剂量对CPP形成和表达均无显著对抗作用，但CBD 80 mg·kg^-1显著抑制METH诱导CPP重建(P<0.05)。结论 CBD对METH的急性效应无明显对抗作用，但显著抑制METH诱导的动机敏化，并干预成瘾记忆的消退学习过程，从而降低成瘾行为重建。     

Y-IP5对小鼠吗啡镇痛、耐受及躯体依赖的影响

目的:评价化合物Y-IP5对小鼠吗啡镇痛、耐受及躯体依赖的影响。方法:采用55℃热板测痛模型分析Y-IP5对小鼠吗啡镇痛和耐受的影响;采用剂量递增法皮下注射吗啡5 d,建立小鼠吗啡依赖模型,评价Y-IP5对小鼠吗啡躯体依赖的影响。结果:在热板测痛模型中,Y-IP5(2.5,5,10 mg.kg-1)不能明显增强小鼠吗啡镇痛作用(P>0.05),Y-IP5(1.25,2.5,5 mg.kg-1)能明显抑制小鼠吗啡镇痛耐受的形成(P<0.05)。伴随吗啡给予Y-IP5(1.25,2.5,5 mg.kg-1)能剂量依赖性地抑制小鼠躯体依赖的形成(P<0.05);在纳洛酮催促前单次给予Y-IP5(1.25,2.5,5 mg.kg-1),不能显著抑制小鼠吗啡躯体依赖的表达(P>0.05)。结论:Y-IP5对吗啡耐受及躯体依赖的形成可能有一定的干预作用。     

眼镜蛇毒粗毒毒素Ⅳ对小鼠吗啡行为敏化的影响

目的 探讨眼镜蛇毒毒素Ⅳ对吗啡行为敏化的影响.方法 测定小鼠自主活动,观察毒素Ⅳ对小鼠自主活动影响.昆明种小鼠慢性吗啡处理,建立吗啡诱导行为敏化模型,观察毒素Ⅳ对吗啡行为敏化影响.结果 毒素Ⅳ(0.027、0.04、0.08 mg/kg)腹腔注射后,均能减少小鼠自主活动,降低吗啡诱导的高活动性,抑制小鼠吗啡行为敏化的获得,阻断小鼠吗啡行为敏化表达,其中中、高剂量毒素Ⅳ作用较显著.结论 毒素Ⅳ对中枢神经系统具有抑制作用,可以阻止吗啡成瘾行为形成,对吗啡诱导的敏化行为具有抑制作用,提示毒素Ⅳ对吗啡精神依赖性可能具有干预作用.     

噻诺啡灌胃给药对小鼠甲基苯丙胺行为敏化的影响

目的:探讨新型丁丙诺啡同系物-噻诺啡,灌胃(ig)给药对小鼠甲基苯丙胺行为敏化过程的影响。方法:测定小鼠的自主活动,观察ig噻诺啡对小鼠的自主活动及单次给予甲基苯丙胺所诱导的小鼠高活动性的影响。建立甲基苯丙胺诱导的小鼠行为敏化模型,观察噻诺啡对行为敏化形成、转化及表达的影响。结果:(1)单次ig噻诺啡(1 2 5 - 5 0mg·kg-1)可剂量依赖性地抑制小鼠的自主活动(P <0 . 0 1) ,其作用多次给药后产生耐受;(2 )噻诺啡对单次给予甲基苯丙胺所诱导的小鼠的高活动性无明显影响;(3)噻诺啡对甲基苯丙胺诱导小鼠行为敏化的形成和表达无明显作用,却可显著抑制敏化的转化过程(P <0 . 0 5 )。结论:ig噻诺啡可抑制小鼠中枢神经系统,阻断甲基苯丙胺诱导小鼠产生行为敏化的转化过程,提示噻诺啡对甲基苯丙胺的成瘾行为具有一定的干预作用。     

ι-四氢巴马汀抑制羟考酮引起小鼠行为敏化的实验研究

目的探讨ι-四氢巴马汀(-tetrahydropalmatine,ι-THP)对羟考酮(oxycodone,oxy)行为敏化的影响和作用机制。方法采用连续7d给小鼠注射羟考酮(5mg.kg-1,ip),停药5d,d13用相同剂量的羟考酮(5mg.kg-1,ip)激发致小鼠行为敏化模型,利用红外光束自主活动测定仪测定小鼠自发活动的实验方法。结果ι-THP(6.25,12.5,18.75mg.kg-1,ig)一次或多次给药,对小鼠的自发活动没有影响,但ι-THP(18.75mg.kg-1,ig)能抑制羟考酮(5mg.kg-1,ip)引起的小鼠行为敏化的形成和表达。阿朴吗啡(0.5、1.0mg.kg-1,ip)给药后50min自身不影响小鼠的自发活动,但阿朴吗啡(1.0mg.kg-1,ip)能翻转ι-THP(18.75mg.kg-1,ig)抑制羟考酮小鼠行为敏化形成的作用,但不影响ι-THP抑制羟考酮行为敏化表达的作用。结论ι-THP抑制羟考酮引起的小鼠行为敏化的形成和表达,ι-THP抑制羟考酮行为敏化的形成可能与抑制DA受体相关,而抑制表达可能与抑制DA受体无关。     

归元片对小鼠吗啡行为敏化的影响

目的 :探讨中药复方制剂归元片对吗啡行为敏化的影响。方法 :测定小鼠的自主活动 ,观察归元片对小鼠自主活动的影响。给小鼠慢性吗啡处理 ,建立吗啡诱导的行为敏化小鼠模型 ,观察归元片对吗啡行为敏化的影响。结果 :(1)归元片 (2 5 - 10g·kg- 1 )明显抑制小鼠的自主活动 ,并呈剂量依赖性 ;(2 )归元片剂量依赖性地阻断小鼠吗啡行为敏化的获得和表达 ,但对行为敏化的转换无影响。结论 :归元片对中枢神经系统具有抑制作用 ,可以阻止吗啡成瘾行为的形成 ,对吗啡诱导的敏化行为具有抑制作用。提示归元片对吗啡的精神依赖性可能具有干预作用     

地高辛对小鼠吗啡行为敏化的影响

目的:探讨地高辛对小鼠吗啡行为敏化的影响.方法:测定小鼠的自主活动,观察地高辛对小鼠自主活动的影响.急性吗啡(10 mg·kg-1,ip)处理小鼠前给予地高辛,观察地高辛对急性吗啡引起小鼠高活动性的影响.慢性吗啡处理小鼠,建立吗啡行为敏化模型,观察地高辛对吗啡行为敏化的影响.结果:(1)地高辛(0.5 mg·kg-1-...     

噻诺啡对小鼠甲基苯丙胺行为敏化的影响

目的:探讨新型阿片受体部分激动剂-噻诺啡对小鼠甲基苯丙胺行为敏化过程的影响。方法:测定小鼠的自主活动,观察噻诺啡对小鼠的自主活动及急性甲基苯丙胺处理所致小鼠活动增强效应的影响。小鼠腹泻注射甲基苯丙胺2mg·kg~(-1)·d~(-1),连续7d,建立甲基苯丙胺诱导的小鼠行为敏化模型,观察噻诺啡对小鼠行为敏化的影响。结果:单次皮下注射噻诺啡(0.0625～1.0mg·kg~(-1))可剂量依赖性地抑制小鼠的自主活动(P<0.05),连续给药7d,噻诺啡对小鼠自主活动的抑制作用不产生敏化,而耐受。噻诺啡对急性甲基苯丙胺处理所致小鼠的高活动性无明显影响。噻诺啡对甲基苯丙胺诱导的小鼠行为敏化的形成和表达无显著作用,但可剂量依赖性地抑制敏化的转化(P<0.05或P<0.01)。结论:噻诺啡对中枢神经系统具有抑制作用,并且可以阻止甲基苯丙胺诱导小鼠产生行为敏化的转化过程,提示噻诺啡可能对甲基苯丙胺的成瘾行为具有一定的干预作用。     

A new buprenorphine analogy, thenorphine, inhibits morphine-induced behavioral sensitization in mice

AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the loco-motor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-adminis     

The role of alpha-adrenoceptor mechanism(s) in morphine-induced conditioned place preference in female mice

It has been shown that the alpha-adrenergic system is involved in some effects of opioids, including analgesia and reward. Gender differences also exist between males and females in response to alpha-adrenergic agents. This study was designed to determine the effects of alpha-adrenoceptor agonists and antagonists on the acquisition or expression of morphine-induced conditioned place preference (CPP) in female mice. The experiments showed that subcutaneous injections of morphine (0.5-8 mg/kg) induced CPP in a dose-dependent manner in mice. Intrapritoneal administration of the alpha-1-adrenoceptor agonist, phenylephrine (0.03, 0.1 and 0.3 mg/kg), and alpha-2 adrenoceptor agonist, clonidine (0.0001, 0.0005 and 0.001 mg/kg), as well as alpha-1-adrenoceptor antagonist, prazosin (0.01, 0.05 and 0.1 mg/kg) or alpha-2 adrenoceptor antagonist, yohimbine (0.005, 0.01 and 0.05 mg/kg) did not induce motivational effects and also did not alter locomotor activity in the animals. In the second set of experiments, the drugs were used before testing on Day 5, to test their effects on the expression of morphine-induced CPP. Intrapritoneal administration of phenylephrine and clonidine decreased the expression of morphine-induced CPP. In contrast, after application of prazosin or yohimbine, the expression of morphine-induced CPP was increased. Administration of lower (0.03 mg/kg) and higher doses of phenylephrine (0.1 and 0.3 mg/kg) during acquisition of morphine CPP decreased and increased the morphine CPP, respectively. Similarly, the administration of prazosin and clonidine decreased while yohimbine increased the morphine CPP. It may be concluded that alpha-adrenoceptor mechanism(s) influence morphine-induced CPP in female mice.     

酸枣仁提取物对小鼠吗啡条件性位置偏爱的影响

目的:观察酸枣仁提取物对吗啡(MOR)诱导建立小鼠条件性位置偏爱(CPP)行为的影响。方法:连续给予吗啡(6mg·kg-1,sc)5d,引起小鼠产生显著的CPP效应,观察酸枣仁提取物对CPP效应的影响。结果:吗啡可诱导小鼠对伴药箱产生显著的位置偏爱;训练阶段于每次给予吗啡前30min给予酸枣仁醇提物800mg·kg-1可拮抗小鼠对吗啡产生的CPP效应(与吗啡对照组比较P<0.05),但酸枣仁醇提物200和400mg·kg-1不影响其效应(P>0.05);酸枣仁乙酸乙酯提取物13mg·kg-1、20mg·kg-1,正丁醇提取物160mg·kg-1可拮抗小鼠对吗啡产生的CPP效应(P<0.05),但酸枣仁石油醚提取物、乙醚提取物、水提物均不影响其效应(P>0.05)。结论:酸枣仁醇提物及其乙酸乙酯提取物、正丁醇提取物能在一定程度上抑制吗啡诱导小鼠建立的CPP行为。     

Effect of imipramine on the expression and acquisition of morphine-induced conditioned place preference in mice

The effect of imipramine and alpha-adrenoceptor agonists and antagonists on the acquisition or expression of morphine-induced conditioned place preference (CPP) was studied in mice. An unbiased CPP paradigm was used to study the effect of the agents. In the first set of experiments, the drugs were used during the development of CPP by morphine or they were used alone in order to see if they induce CPP or conditioned place aversion (CPA). Our data showed that intraperitoneal injection of morphine sulphate (2.5-10 mg/kg) induced CPP in mice. Imipramine (0.5-2.5 mg/kg), phenylephrine (0.5-2 mg/kg), yohimbine (0.5-2 mg/kg) or prazosin (0.1-1 mg/kg) did not influence CPP, but clonidine (0.002-0.05 mg/kg) induced CPA. Yohimbine increased, while clonidine and prazosin reversed, morphine-induced CPP. Phenylephrine did not influence the CPP induced by morphine. In the second set of experiments, when the drugs were used before testing on Day 6, in order to test their effects on the expression of morphine-induced CPP, imipramine (0.5-5 mg/kg) reversed morphine-induced CPP and this reversal was blocked by naloxone (2 mg/kg). Clonidine and prazosin reversed, while yohimbine decreased morphine-induced CPP. Phenylephrine did not alter the morphine response. Furthermore, yohimbine and prazosin reversed the imipramine effect. None of the drugs influenced locomotion. However, prazosin or yohimbine in combination with morphine altered locomotor activity during the acquisition of CPP. Yohimbine by itself increased locomotion. It is concluded that imipramine can induce CPA through an opioid receptor mechanism and alpha-adrenoceptor agents may influence morphine CPP.     

大鼠吗啡精神依赖时伏核和前额叶皮质中NR2A、NR2B表达的变化

目的:建立条件性位置偏爱(CPP)模型,检测吗啡精神依赖大鼠伏核和前额叶皮质N-甲基-D-天冬氨酸受体(NMDA受体)调节亚基NR2A、NR2B表达的变化。方法:使用盐酸吗啡建立大鼠CPP。CPP形成后,每组大鼠5只灌注固定后进行免疫组织化学形态学检测,3只断头处死取伏核和前额叶皮质,并提取细胞膜蛋白进行Western blot定量检测。结果:吗啡诱导大鼠形成CPP时,前额叶皮质和伏核中NR2B有明显变化,免疫组织化学结果显示NR2B阳性细胞数明显增高(前额叶皮质P<0.05,伏核P<0.01)。Western blot结果显示NR2B蛋白表达量明显上调(前额叶皮质P<0.05,伏核P<0.01),而NR2A则无明显改变。结论:使用吗啡建立的大鼠CPP模型中,NMDA受体调节亚基NR2B在与奖赏作用密切相关脑区伏核和前额叶皮质中均有明显变化,而NR2A则无明显改变,表明NMDA受体中NR2B调节亚基在吗啡精神依赖形成中发挥着重要作用。