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。     

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。     

归元片对小鼠甲基苯丙胺行为敏化的影响

目的:探讨中药复方制剂归元片对甲基苯丙胺行为敏化的影响.方法:测定小鼠的自主活动,观察归元片对小鼠自主活动及甲基苯丙胺急性活动增强效应的影响.小鼠慢性甲基苯丙胺处理,建立甲基苯丙胺诱导的行为敏化小鼠模型,观察归元片对甲基苯丙胺行为敏化获得和表达的影响.结果:归元片呈剂量依赖性降低小鼠的活动性,对甲基苯丙胺的急性高活动效应有抑制作用.归元片阻断小鼠甲基苯丙胺行为敏化的获得和表达.结论:归元片对中枢神经系统功能具有抑制作用,能抑制甲基苯丙胺行为敏化的获得和表达,提示归元片能抑制甲基苯丙胺的奖赏效应,可能对防治甲基苯丙胺的滥用和成瘾有效.     

甲基苯丙胺诱导小鼠行为敏化模型的构建与评估

目的:探讨不同剂量水平甲基苯丙胺(MA)所诱导的小鼠行为敏化模型的构建与评估方法。方法:40只C57BL/6J小鼠,随机分为5组:生理盐水对照组(NS)和0.5、2、5、10mg·kg-1MA剂量组,各组在形成期连续5d每天腹腔注射(ip)不同剂量药物并记录自主活动情况,转化期停药观察2d后,在d8表达期给予最后一次等量剂量MA,并记录自主活动情况。结果:(1)不同剂量MA作用于实验小鼠,在小剂量水平即能够诱导出明显的行为敏化现象,且随着药物浓度增大,呈现剂量依赖性变化;(2)在10mg·kg-1大剂量水平,小鼠表现为明显的刻板行为,在表达期同样出现了刻板行为的增强现象。结论:本实验为不同剂量的小鼠MA敏化模型提供了比较标准的构建和评估方法;2mg·kg-1MA作用于实验小鼠,诱导出了明显的行为敏化现象,同时其他精神运动改变如刻板行为出现较少,是构建药物依赖行为敏化模型较理想的剂量;利用该行为敏化模型可进一步分析和评估药物依赖治疗性药物的疗效。     

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。     

HPLC法测定盐酸噻诺啡片的含量及其溶出度

目的:建立一种HPLC法测定盐酸噻诺啡片的含量及溶出度.方法:采用Phenex prodigy C18色谱柱(250mm×4.6mm,5μm),以乙腈-甲醇-0.02mol·L-1磷酸盐缓冲液(pH=3,含0.2%的三乙胺)(40:15:45)为流动相,220nm为检测波长,测定了盐酸噻诺啡片的含量和溶出度.结果:本法测定盐酸噻诺啡的线性范围为0.5～10μg·mL-1(r=0.999 9);日内精密度和日间精密度均小于2%(n=5);回收率在98%～102%之间.结论:本法精密、准确,适用于盐酸噻诺啡片的含量及溶出度测定.     

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-...     

多巴胺D3受体激动剂和拮抗剂减弱甲基苯丙胺诱导的行为敏化

目的 通过研究多巴胺D3受体(dopamine D3 receptor, D3R)激动剂ML417和拮抗剂GSK598809对甲基苯丙胺(methamphetamine, METH)诱导的小鼠行为敏化的影响,探讨D3R在METH成瘾中的调控作用。方法 以D3R基因敲除(D3R-/-)小鼠以及具有相同遗传背景的野生型(WT)小鼠为研究对象,采用行为敏化模型,观测D3R激动剂ML417和拮抗剂GSK598809对METH诱导的行为敏化的影响。结果 D3R激动剂ML417(1 mg/kg, ip)和拮抗剂GSK598809(5 mg/kg、10 mg/kg, ip)均可减弱METH(2 mg/kg, ip)诱导的WT小鼠行为敏化(P<0.05),但在对照组D3R-/-小鼠中并无此作用。结论 D3R激动剂ML417和拮抗剂GSK598809均可通过单一激动或拮抗D3R的方式,减弱METH诱导的WT小鼠行为敏化,D3R可能成为治疗METH成瘾的一个靶点。     

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。     

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     

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.     

条件性位置偏爱形成对小鼠吗啡行为敏化的影响

目的研究条件性位置偏爱对小鼠吗啡行为敏化的影响。方法应用计算机视频分析系统观察吗啡和氟哌啶醇对雄性小鼠单位时间内的总活动度的影响。同时观察条件性位置偏爱形成后,小鼠单位时间内的总活动度、平均速度和穿梭次数的改变。结果吗啡给药后显著增加小鼠单位时间内的总活动度,氟哌啶醇使小鼠总活动度减少,并且对抗吗啡引起的总活动度的增加。条件性位置偏爱形成后,吗啡组小鼠在白箱停留的时间显著增加,但总活动度、平均速度和穿梭次数与训练前相比显著减少。结论氟哌啶醇可抑制吗啡诱导的行为敏化,条件性位置偏爱形成后可能引起多巴胺系统功能降低。     

Effects of histamine agents on methamphetamine-induced stereotyped behavior and behavioral sensitization in rats

In this study, effects of histamine (HA) agents on methamphetamine (METH)-induced stereotyped behavior and behavioral sensitization were examined in rats. Pretreatment with a precursor of HA, L-histidine (750 mg/kg), significantly inhibited the METH (3 mg/kg)-induced stereotyped behavior, whereas pretreatment with an inhibitor of HA synthesis, α-fluoromethylhistidine (FMH) (100 mg/kg), an H₁ antagonist pyrilamine (5 mg/kg) or an H₂ antagonist zolantidine (5 mg/kg) enhanced it. The inhibitory effect of L-histidine on METH-induced stereotyped behavior was significantly blocked by coadministration of pyrilamine and zolantidine, indicating that the effect is mediated through H₁ and H₂ receptors. Moreover, chronic treatment with METH (3 mg/kg) significantly enhanced stereotyped behavior at the rechallenge with METH (1 mg/kg). Chronic treatment with L-histidine (750 mg/kg) plus METH inhibited the METH-induced argumentation of stereotyped behavior, while that with FMH (100 mg/kg), pyrilamine (5 mg/kg) or zolantidine (5 mg/kg) potentiated it. These findings suggest that the HA neuron system has an inhibitory role in METH-induced stereotyped behavior and behavioral sensitization. Received: 1 July 1996/Final version: 26 November 1996     

Potentiating effect of tramadol on methamphetamine-induced behavioral sensitization in mice

Rationale Polydrug abuse is a common phenomenon in human drug addicts. Previous studies have shown that both tramadol (TRAM) and methamphetamine (METH) share the ability to modulate brain monoaminergic (dopamine, 5-hydroxytryptamine, and noradrenaline) systems that may be involved in behavioral sensitization to METH. Therefore, we hypothesized that there would be an interaction between TRAM and METH on behavioral sensitization induced by METH. Objectives To investigate whether TRAM affects METH-induced behavioral sensitization. Methods Male Kunming mice were subjected to two regimens of drugs: (1) Mice were injected with TRAM (1–16 mg/kg, i.p.) alone or a combination of TRAM and METH (1 mg/kg, i.p.) once daily for 7 days. After 7 drug-free days (on day 15), animals were challenged with the corresponding TRAM dose or METH (1 mg/kg, i.p.). On days 1, 7, and 15, locomotion was monitored in the open field test after the last injection. (2) Mice received METH (1 mg/kg, i.p.) once daily for 7 days, followed by 7 drug-free days. On day 15, a challenge of TRAM (1–16 mg/kg, i.p.) or TRAM plus METH (1 mg/kg, i.p.) was given and then locomotor activity was quantified. Results TRAM or METH challenge did not induce hyperlocomotion in mice chronically treated with TRAM, and TRAM challenge was insufficient to induce subsequent hyperlocomotion in METH-sensitized mice. However, TRAM significantly increased METH-induced hyperlocomotion. TRAM plus METH-sensitized mice showed a significantly greater hyperlocomotor response to METH challenge than METH-sensitized mice. Furthermore, TRAM (16 mg/kg, i.p.) plus METH (1 mg/kg, i.p.) challenge enhanced the sensitized locomotor response compared to METH-alone (1 mg/kg, i.p.) challenge in METH-sensitized mice. Conclusions TRAM fails to produce behavioral sensitization, and there is no apparent cross-sensitization between TRAM and METH. However, TRAM can increase METH-induced hyperlocomotion and potentiate the development and expression of behavioral sensitization to METH.     

Effects of selective D-1 and D-2 dopamine antagonists on development of methamphetamine-induced behavioral sensitization

The present study examined effects of selective antagonists of D-1 and D-2 dopamine receptors on the development of behavioral sensitization produced by repeated methamphetamine (MAP) administration. Male Sprague-Dawley rats were divided into four groups. Each group received a daily injection of saline (control group), 4 mg/kg MAP (MAP group), 1 mg/kg YM-09151-2 plus 4 mg/kg MAP (YM+MAP group) or 0.5 mg/kg SCH 23390 plus 4 mg/kg MAP (SCH+MAP group) for 14 days. During daily injection for 14 days, the MAP group exhibited a progressive augmentation in locomotor and stereotyped behavior, whereas the progression of such behaviors in the YM+MAP and SCH+MAP group was completely prevented. After an abstinence period of 7 days, all groups received a challenge of 2 mg/kg MAP. The MAP challenge reproduced hyperlocomotion and intense stereotyped behavior only in the MAP group. However, neither the YM+MAP group nor the SCH+MAP group showed sterotypy. The manner in which both groups showed only hyperlocomotion was similar to that observed in the control group. These results indicate that both selective D-1 antagonists and selective D-2 antagonists not only reverse MAP-induced motor effects at each injection but also prevent the development of behavioral sensitization induced by repeated MAP administration.     

行为敏化动物模型在药物依赖性评价中的应用

药物滥用和成瘾呈上升趋势。它既是一个严重的社会问题 ,又是一个非常重要的医学问题。因此 ,对作用于中枢神经系统的药物进行依赖性评价具有十分重要的意义。研究资料表明药物敏化与药物滥用和成瘾具有密切的关系 ,依赖性药物致敏化的药理学特性越来越受到重视。本文介绍了行为敏化动物模型建立的方法 ,阐述了行为敏化形成和表达的神经生物学机制 ,着重探讨了行为敏化动物模型在药物依赖性评价中的作用。