钩藤碱对苯丙胺依赖大鼠神经核团中NR2B mRNA表达的影响

目的研究钩藤碱对苯丙胺诱导的条件性位置偏爱大鼠伏核和杏仁核中NR2B mRNA表达的影响。方法将56只♂SPF级SD大鼠分为正常对照组、苯丙胺模型组、氯胺酮+苯丙胺组、钩藤碱低、中、高剂量+苯丙胺组和钩藤碱+生理盐水组,每组8只。按要求分别给予相应药物。d5用条件性位置偏爱箱观察大鼠在白箱中的停留时间,并用原位杂交技术对伏核和杏仁核NR2B mRNA表达进行检测。结果①连续4d给予苯丙胺2mg.kg-1建立了位置偏爱模型,氯胺酮及钩藤碱低、中、高剂量均可消除位置偏爱效应,随钩藤碱剂量增加效应加强,且钩藤碱自身无精神依赖性;②苯丙胺模型大鼠伏核和杏仁核NR2B mRNA表达较正常对照大鼠明显增加,氯胺酮及中、高剂量钩藤碱抑制NR2B mRNA的表达,低剂量无明显影响。钩藤碱本身不影响正常大鼠NR2B mRNA的表达。结论伏核和杏仁核NR2B mRNA的表达参与了钩藤碱抗苯丙胺依赖作用的分子生物学机制。     

钩藤碱对苯丙胺依赖大鼠伏核和杏仁核中NR2B蛋白表达的影响

目的:研究钩藤碱对苯丙胺依赖大鼠伏核和杏仁核中NR2B蛋白表达的影响。方法:采用条件性位置偏爱实验和免疫组化技术。结果:(1)建立了苯丙胺(2mg.kg-1,连续4d)诱导的位置偏爱模型,氯胺酮及钩藤碱低、中、高剂量均可消除苯丙胺诱导的位置偏爱效应,随钩藤碱剂量增加其效应加强,且本身无精神依赖性;(2)苯丙胺模型组大鼠伏核和杏仁核NR2B蛋白表达增加,氯胺酮及钩藤碱中、高剂量抑制NR2B表达,低剂量及本身对NR2B表达无影响。结论:伏核和杏仁核NR2B蛋白表达参与了钩藤碱抗苯丙胺依赖作用的分子机制。     

青藤碱对吗啡依赖小鼠位置偏爱效应的影响

目的 :利用条件性位置偏爱实验研究中药成分青藤碱对小鼠吗啡奖赏效应的影响。方法 :实验采用有倾向性程序。吗啡 (9mg· kg-1,sc,每日 1次 ,5 d)引起小鼠显著的位置偏爱效应。在训练阶段每天 sc吗啡前3 0 min预先给予青藤碱 (1 0 ,3 0和 60 mg· kg-1,ip)可剂量依赖性地抑制吗啡引起的小鼠位置偏爱效应。结果 :提示预先给予青藤碱能消除吗啡产生的条件性位置偏爱。     

钩藤碱对苯丙胺依赖大鼠脑内氨基酸类神经递质含量的影响

目的:观察钩藤碱对苯丙胺依赖大鼠脑内氨基酸类神经递质含量的影响。方法:采用条件性位置偏爱实验和脑电超慢涨落分析技术。结果:氯胺酮和钩藤碱均能消除苯丙胺导致的位置偏爱效应;苯丙胺使大鼠呈现完全偏离的“脑功能平衡图”,氯胺酮和钩藤碱可使其恢复至平衡态;苯丙胺导致大鼠脑内抑制性氨基酸含量明显下降(P<0.01),兴奋性氨基酸含量明显上升(P<0.01),氯胺酮和钩藤碱均可恢复其至正常水平,钩藤碱本身对这些均无影响。结论:钩藤碱可调整苯丙胺引起的大鼠脑内氨基酸神经递质含量的异常变化。     

青风藤及青藤碱对吗啡依赖小鼠位置偏爱效应及cAMP水平的影响

目的观察中药青风藤及其有效成分青藤碱对吗啡诱导的小鼠位置偏爱效应的影响及其与中枢cAMP水平的关系.方法连续给予吗啡 (9mg/kg, 1次/d,sc) 5d,引起小鼠产生显著的条件性位置偏爱效应.用两种方式给予青风藤醇提液(5,10g/kg, ig)和青藤碱 (60mg/kg, ig) ,即在训练阶段每天sc吗啡前 45min给予和在d 6测定位置偏爱前45min仅给药一次.大脑皮层cAMP含量采用放射免疫法测定. 结果吗啡对照组小鼠在伴药箱中停留的时间明显延长, 小鼠脑组织的cAMP水平亦显著升高. 青风藤或青藤碱连续用药可显著抑制吗啡引起的小鼠位置偏爱的形成,对小鼠已形成的条件性位置偏爱效应也具有一定的抑制作用.并能降低脑内cAMP含量.结论青风藤及青藤碱能消除吗啡产生的条件性位置偏爱,其作用机制与降低中枢cAMP水平有关.     

粉防己碱对小鼠吗啡位置偏爱效应的影响(英文)

利用条件性位置偏爱实验研究钙拮抗剂粉防己碱对小鼠吗啡奖赏效应的影响 .实验采用有倾向性程序 .吗啡 ( 5mg· kg-1,sc,每日 1次 ,5d)引起小鼠显著的位置偏爱效应 .在训练阶段每天 sc吗啡前 30 min预先给予粉防己碱 ( 1 0 ,2 0和 40 mg·kg-1,ip)可剂量依赖性地抑制吗啡引起的小鼠位置偏爱效应 .而粉防己碱 ( 1 0 ,2 0和 40 mg· kg-1,ip)只在测试前 30 min给药 1次 ,不影响吗啡已形成的小鼠位置偏爱 .结果说明粉防己碱能有效地抑制吗啡偏爱效应的获得 ,但不影响其表达 .     

青风藤及青藤碱对吗啡依赖小鼠位置偏爱效应及cAMP水平的影响

目的　观察中药青风藤及其有效成分青藤碱对吗啡诱导的小鼠位置偏爱效应的影响及其与中枢cAMP水平的关系。方法　连续给予吗啡(9mg/kg ,1次/d ,sc) 5d ,引起小鼠产生显著的条件性位置偏爱效应。用两种方式给予青风藤醇提液(5 ,10g/kg ,ig)和青藤碱(60mg/kg ,ig) ,即在训练阶段每天sc吗啡前4 5min给予和在d6测定位置偏爱前4 5min仅给药一次。大脑皮层cAMP含量采用放射免疫法测定。结果　吗啡对照组小鼠在伴药箱中停留的时间明显延长,小鼠脑组织的cAMP水平亦显著升高。青风藤或青藤碱连续用药可显著抑制吗啡引起的小鼠位置偏爱的形成,对小鼠已形成的条件性位置偏爱效应也具有一定的抑制作用。并能降低脑内cAMP含量。结论　青风藤及青藤碱能消除吗啡产生的条件性位置偏爱,其作用机制与降低中枢cAMP水平有关     

氯胺酮诱导大鼠条件性位置偏爱的消退特点

目的:探讨氯胺酮在大鼠模型上形成的条件性位置偏爱(CPP)的消退特点。方法:24只SD♂大鼠随机分为3组:对照组、氯胺酮依赖自然消退组和氯胺酮依赖训练消退组,每组8只。氯胺酮依赖组交替隔天腹腔注射氯胺酮和等容量生理盐水16d使大鼠形成条件性位置偏爱,对照组每天给予等容量生理盐水。在实验的d18,CPP形成后氯胺酮(10-15mg.kg-1)依赖训练消退组进行生理盐水消退训练,然后各组分别在不同时段(d19,d24-26,d54-56)进行CPP测试。结果:氯胺酮处理的大鼠出现了明显的CPP,自然消退组大鼠CPP在训练后d38仍存在,训练消退组经生理盐水消退训练后大鼠CPP迅速消失。结论:氯胺酮诱导的大鼠CPP可维持38d以上,生理盐水消退训练可加速其消退。     

NMDA受体拮抗剂氯胺酮对苯丙胺类中枢兴奋剂条件性位置偏爱效应的影响

目的研究单独使用甲基苯丙胺(methamphetamine,MA)或氯胺酮及两者联合给药致小鼠条件性位置偏爱(conditioned place preference,CPP)效应及停药后和停药后重激发的位置偏爱的变化情况。方法36只♂昆明小鼠分为4组,分别为生理盐水对照组(10ml·kg-1,ip)、MA给药组(2mg·kg-1,ip)、氯胺酮给药组(15mg·kg-1,ip)、MA与氯胺酮合用组(MA2mg·kg-1,ip;氯胺酮15mg·kg-1,ip,提前30min注射)。采用倾向性训练程序训练小鼠,训练8d,隔天进行药物匹配训练,隔天生理盐水训练。停药24d后,氯胺酮组和两药合用组位置偏爱消失后,d25采用训练期时所用药物一半的剂量进行激发。分别记录15min之内小鼠各阶段在伴药侧停留的时间。结果MA或氯胺酮单独使用以及两者联合给药均可使小鼠出现CPP。氯胺酮的CPP效应维持时间较短,停药d9已消失,同时可抑制MA的CPP持续时间,两组再次激发均不重现。MA组小鼠位置偏爱在停药后25d里并未消失,激发后可使该效应显著增强。结论氯胺酮也是一种能够促使小鼠产生位置偏爱的药物,停药后短期内可增强MA引起位置偏爱的强度,但可抑制CPP的维持时间,同时抑制MA再激发后CPP重现。     

氯胺酮诱导的大鼠条件性位置偏爱

目的:探讨氯胺酮在大鼠模型上形成条件性位置偏爱(CPP)的特点,分析氯胺酮精神依赖性潜力。方法:(1)60只SD♂大鼠随机分为对照组、氯胺酮及吗啡阳性对照组。(2)氯胺酮组每隔24h腹腔注射氯胺酮10m·lkg-1一次,连续6d,建立大鼠氯胺酮精神依赖性模型,吗啡组给予等剂量的吗啡,对照组则给予等剂量的生理盐水;(3)氯胺酮组及吗啡组于CPP形成后给予生理盐水进行消退实验。结果:(1)氯胺酮组及吗啡组大鼠出现了明显的CPP;(2)与吗啡组相比,氯胺酮组的CPP效应更显著,但消退较快。结论:氯胺酮可诱导大鼠产生CPP,但随着时间的推移CPP消退速度较吗啡快。     

Rhynchophylline down-regulates NR2B expression in cortex and hippocampal CA1 area of amphetamine-induced conditioned place preference rat

N-methyl-D-aspartate receptor 2B subunit (NR2B) has an important role in the development of conditioned place preference (CPP) and psychostimulant abuse. Rhynchophylline is presently used to treat central nervous systems diseases and has a non-competitive antagonistic effect on NMDA receptors. In this study, amphetamine was administered in rats (2 mg/kg, s.c., once each day for 4 consecutive days), during which they were treated with rhynchophylline (60 mg/kg, i.p., once each day for the next 3 days). NR2B mRNA and protein expression were examined by in situ hybridization and immunohistochemistry. CPP was induced by amphetamine (2 mg/kg, s.c.) by 4th day in rats. Rhynchophylline effectively reversed the expression of amphetamine-induced CPP and itself did not produce a CPP. Amphetamine-CPP rats showed a significantly increased NR2B mRNA and protein expression in medial prefrontal cortex and hippocampal CA1 areas as compared to the control group. Rhynchophylline reversed NR2B mRNA and protein levels induced by amphetamine but rhynchophylline by itself had no effect on NR2B expression in control rats. These results indicate that rhynchophylline inhibits the expression of amphetamine-induced rewarding effect, and this action might be related to down-regulation of NR2B expression in medial prefrontal cortex and hippocampal CA1 area.     

Cannabinoid CB(1) receptor antagonist rimonabant attenuates reinstatement of ketamine conditioned place preference in rats

Recent evidence suggests that cannabinoid CB(1) receptors may represent effective targets for therapeutic agents used to treat cocaine and heroin relapse. However, the role of cannabinoid CB(1) receptors in the potential treatment for other drugs of abuse is still largely unknown. The present study was conducted to determine whether cannabinoid CB(1) receptors play a similar role in relapse to ketamine abuse. To establish a ketamine reinstatement model in the conditioned place preference paradigm, rats were trained to develop place preference conditioned by ketamine, which was subsequently extinguished through daily exposure to the test chambers in the absence of ketamine. On the day following the last extinction session, four groups of rats were injected with ketamine (1, 5, 10 and 15 mg/kg, i.p.) to reinstate previously extinguished conditioned place preference. To investigate the effects of rimonabant, a cannabinoid CB(1) receptor antagonist, on reinstatement of ketamine-induced place preference, different doses of rimonabant (0.1, 0.5 and 3 mg/kg, i.p) were injected 30 min prior to the ketamine (5 and 15 mg/kg, i.p.) priming injection in a separate group of rats. To determine whether rimonabant itself produces conditioned place preference or conditioned place aversion, rats were trained for conditioned place preference or place aversion with rimonabant (0, 0.1, 0.5, 3.0 mg/kg, i.p.). While ketamine priming injections reinstated extinguished place preference, rimonabant administration significantly attenuated the reinstatement of ketamine-induced place preference in a dose-dependent manner. Importantly, rimonabant itself did not produce conditioned place preference or place aversion. Since the reinstatement effects of ketamine administration were inhibited by rimonabant, these findings suggest that a cannabinoid CB(1) receptor antagonist may be useful in preventing relapse to ketamine abuse.     

东莨菪碱对吗啡依赖大鼠条件位置性偏爱激活的抑制作用

目的:观察东莨菪碱(Scopolamine,Sco)对吗啡(Morphine,Mor)依赖大鼠条件位置性偏爱激活的抑制作用。方法:以剂量递增连续皮下(SC)给吗啡6天建立吗啡诱导大鼠条件位置性偏爱(CPP)模型,第7天用生理盐水替代吗啡训练大鼠10天,使形成的CPP逐渐消退,单次SC4mg/kg吗啡激发消退的CPP。部分大鼠在注射吗啡前30分钟分别腹腔注射(ip)Sco(1mg/kg、2mg/kg、3mg/kg)。观察东莨菪碱对吗啡依赖大鼠在伴药箱停留时间的变化。结果:与Mor依赖组相比在SC4mg/kgMor引燃刺激前30min应用Sco1mg/kg、2mg/kg、3mg/kg均可以使大鼠在伴药箱停留时间缩短(P<0.05)。结论:Sco一定程度上抑制Mor引燃的Mor依赖大鼠的条件位置性偏爱激活。     

Amphetamine locomotor sensitization and conditioned place preference in adolescent male and female rats neonatally treated with quinpirole

Neonatal quinpirole treatment has been shown to produce an increase in dopamine D2-like receptor sensitivity that persists throughout the subject's lifetime. The objective was to analyze the effects of neonatal quinpirole treatment on effects of amphetamine in adolescent rats using locomotor sensitization and conditioned place preference procedures. Sprague-Dawley rats were treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1 to P11 and raised to adolescence. For locomotor sensitization, subjects were given amphetamine (1 mg/kg) or saline every second day from P35 to P47 and were placed into a locomotor arena. In female rats, neonatal quinpirole treatment enhanced amphetamine locomotor sensitization compared with quinpirole-free controls sensitized to amphetamine. Male rats demonstrated sensitization to amphetamine, although this was muted compared with female rats, and were unaffected by neonatal quinpirole. For conditioned place preference, subjects were conditioned for 8 consecutive days (P32-39) with amphetamine (1 mg/kg) or saline and a drug-free preference test was conducted at P40. Rats treated with neonatal quinpirole enhanced time spent in the amphetamine-paired context compared with quinpirole-free controls conditioned with amphetamine, but only female controls conditioned with amphetamine spent more time in the drug-paired context compared with saline-treated controls. Increased D?-like receptor sensitivity appears to have enhanced the behavioral effects of amphetamine, but these effects were more prevalent in adolescent female rats compared with male rats.     

Effects of melatonin in a place preference conditioning depend on the time of administration

A conditioned place preference paradigm was used to assess potential rewarding properties of melatonin. The conditioning with melatonin was carried out at two periods of the 12-h light/dark cycle: in the morning (08.30-10.00) and in the evening (18.30-20.00). Morning administration of melatonin (2.5, 5 and 10 mg/kg) did not support conditioned place preference. In contrast, evening conditioning with melatonin caused a clear shift towards the drug-paired side. This effect was dose-dependent; higher doses of 2.5, 5, 10 and 50 mg/kg induced conditioned preference while lower doses of 0.5 and 1 mg/kg were ineffective. The increase in the side preference induced by the two most effective doses of melatonin (10 and 50 mg/kg) were comparable to that induced by 1 mg/kg of amphetamine, and was significantly attenuated by the melatonin antagonist, S 22153 (20 mg/kg). In chronic experiment, melatonin (10 mg/kg) caused similar increase of the time spent on conditioned side both in animals administered vehicle for 7 days and in rats receiving 10 mg/kg of melatonin for the same period of time. Potent activity in the conditioned preference model suggests that melatonin may have rewarding properties, which moreover, is not tolerated following repeated pre-exposure to the drug. These findings may indicate potential abuse liability of melatonin, and therefore, its use by humans should require a careful monitoring for abuse and/or dependency.     

Memantine and ACPC affect conditioned place preference induced by cocaine in rats

The influence of uncompetitive NMDA receptor antagonist, 1-amino-3,5--dimethyl-adamantane (memantine) and partial glycineB site agonist, 1-amino-cyclopropanecarboxylic acid (ACPC) on cocaine-induced conditioned place preference (CPP) were examined in male Wistar rats. After determination of initial preference, animals were conditioned with cocaine (5 mg/kg, ip) for 3 conditioning trials, alone or in combination with memantine (7.5 mg/kg, ip) or ACPC (50.0 mg/kg, ip). Memantine prevented acquisition and expression of the place preference produced by cocaine, while ACPC prevented only acquisition effect. Neither of the NMDA antagonists displayed any reinforcing properties by itself. Our current data suggest that the NMDA receptor complex may be involved in the rewarding effect of cocaine.