MK-801与环境线索交互作用对吗啡行为敏感化的影响

为探讨MK-801与环境线索交互作用对吗啡诱导行为敏感化的影响,将42只大鼠随机分为对照组,MK-801组,吗啡组（匹配和非匹配）和MK-801+吗啡组（匹配和非匹配）。行为敏感化模型建立分为发展期,戒断期和表达期三个阶段。实验结果发现：同时给予MK-801（0.1mg·kg-1）会促进吗啡（5mg·kg-1）诱导大鼠行为敏感化的发展,而且会使MK-801成为大鼠行为敏感化表达所必需的条件性刺激。MK-801的内部线索作用过强,从而削弱了环境的外部线索作用。研究结果表明：MK-801对吗啡诱导行为敏感化的影响存在状态依赖（state-dependency）现象,提示在NMDA受体与行为敏感化关系的研究中应考虑选择刺激特性更小的药物     

毒扁豆碱对吗啡导致的大鼠行为敏感化的抑制作用

药物滥用导致的行为敏感化被认为与成瘾过程密切相关。本实验探讨吗啡导致的大鼠行为敏感化与神经递质乙酰胆碱的关系。实验动物分为3组,分别进行生理盐水、吗啡（10.0mg/kg）、吗啡（10.0mg/kg）＋胆碱酯酶抑制剂毒扁豆碱（0.2mg/kg）前处理,36小时腹腔注射4次。前处理结束1周所有动物注射小剂量吗啡（4.0mg/kg）;使用生理盐水前处理的动物,第2周注射毒扁豆碱（0.2mg/kg）;使用吗啡前处理的动物,第2周注射小剂量吗啡＋毒扁豆碱（0.2mg/kg）,第3周再次注射小剂量吗啡。动物每次接受注射后立即记录其在两小时内的活动量(10分钟为一个记录单元)。结果表明,毒扁豆碱既能够抑制吗啡诱导的行为敏感化,也能够阻断小剂量吗啡对行为敏感化的“点燃”作用。由此推论,吗啡导致的行为敏感化与其抑制乙酰胆碱分泌有关。     

冲动性对吗啡诱导的条件性位置偏爱及行为敏感化的影响

许多研究显示, 冲动性与尼古丁、可卡因、海洛因等药物成瘾显著相关, 但它对吗啡成瘾的影响尚未见到报道。本实验考察冲动性对吗啡诱导的条件性位置偏爱及行为敏感化的影响。实验采用延迟奖赏模型将大鼠的冲动性区分为高、中、低三个水平, 每个水平设置吗啡处理组和盐水处理组。结果发现：动物对吗啡诱导的条件性位置偏爱的程度表现为低冲动组>中冲动组>高冲动组, 并且中、低冲动组动物形成了条件性位置偏爱而高冲动组没有形成这种偏爱; 在行为敏感化表达期, 与相应的盐水组比较, 高、中冲动组动物的吗啡运动激活效应显著, 而低冲动组没有达到显著水平。这些结果提示, 条件性位置偏爱任务中, 动物的冲动性越高, 吗啡的强化效应越低; 行为敏感化任务中, 动物的冲动性越高, 吗啡的运动激活效应越高。由此可见, 动物的冲动性对吗啡诱导的条件性位置偏爱及行为敏感化的影响存在差异。     

石杉碱甲对应激诱导的吗啡行为敏感化表达的影响

为探讨石杉碱甲对应激诱导的吗啡行为敏感化表达的影响, 将40只动物随机分为5组: 盐水组、石杉碱甲组、吗啡组、应激组、石杉碱甲+应激组。实验发现, 急性/慢性空瓶应激都能够激发吗啡行为敏感化的表达, 而石杉碱甲能够显著抑制空瓶应激的这种激发作用。经过吗啡点燃后, 急性空瓶应激并不能显著影响动物的行为敏感化, 提示与成瘾性药物的再现相比, 空瓶应激对动物的影响力度较小。研究结果表明, 石杉碱甲能够抑制急性/慢性空瓶应激诱导的吗啡行为敏感化表达, 表明这类胆碱酯酶抑制剂有可能成为治疗药物依赖的潜在药物。     

东莨菪碱对吗啡诱导的大鼠行为敏感化的影响

药物重复处理导致的行为敏感化与成瘾过程密切相关。本实验检验东莨菪碱对吗啡诱导的大鼠行为敏感化发展和转化的影响。实验一动物分为3组,分别进行生理盐水（对照组）、吗啡（10mg/kg,吗啡组）、吗啡（10mg/kg）＋东莨菪碱（3mg/kg,吗啡-东莨菪碱组）前处理,36小时腹腔注射4次（第1~2天）。自然戒断7天（第3~9天）。第10天,所有动物均使用吗啡（4mg/kg）激发,记录动物的自发活动量;第24天,吗啡组和吗啡-东莨菪碱组动物重复第10天的操作。实验二动物分为3组,分别接受生理盐水（对照组）、吗啡（10mg/kg,吗啡组）、吗啡（10mg/kg,吗啡-东莨菪碱组）处理,36小时腹腔注射4次（第1~3天）;间隔12小时后,3组动物分别接受生理盐水、生理盐水和东莨菪碱（3mg/kg）处理,仍为36小时腹腔注射4次（第3 ~5天）。第6~9天不进行药物处理。第10天和第17天,分别使用吗啡（4mg/kg）激发,记录动物的活动量。记录时间均为两小时(10分钟为一个记录单元)。结果表明,东莨菪碱能够抑制吗啡诱导的行为敏感化的发展,一定程度上也能够延缓行为敏感化的转化但没有阻断这种转化     

小剂量吗啡对大鼠活动性的影响

腹腔注射不同剂量吗啡,观察各组大鼠在给药后不同时间的活动性（ｌｏｃｏｍｏｔｏｒａｃｔｉｖｉｔｙ,ＬＡ）,连续给药８天,每天给药后９５ｍｉｎ内,每间隔１５ｍｉｎ,记录大鼠５ｍｉｎ内在限定空间中所走格数。结果表明：随吗啡给药剂量或次数增加,ＬＡ呈升高趋势;使大鼠ＬＡ明显兴夯的适宜低剂量为４ｍｇ／ｋｇ／ｄａｙ,该剂量下每天药后１５－２０ｍｉｎＬＡ为峰值,而且此时段ＬＡ逐日升高,至第８日出现下降趋势,此毕     

吗啡对不同距离条件下大鼠信号追踪和目标追踪的影响

条件刺激短暂呈现并消失后, 奖赏立即呈现, 多次匹配后诱导出动物对条件刺激(信号追踪)或奖赏呈现装置如食盒(目标追踪)的接近。条件刺激与食盒间的距离是影响信号/目标追踪反应和损害联结学习的重要变量, 成瘾药物能够增加奖赏的诱因动机, 进而增加个体的奖赏寻求行为。距离能否通过损害联结学习而减弱成瘾药物的动机放大作用尚未见到报道。本实验采用autoshaping模型, 考察8、30和60 cm距离条件下吗啡处理对大鼠信号追踪和目标追踪的影响。结果发现：(1)信号追踪随距离增加而减少, 目标追踪对距离不敏感。(2)急性吗啡处理减少8、30和60 cm条件下信号追踪而增加8和60 cm条件下目标追踪, 慢性吗啡处理在8和30 cm条件下减少信号追踪增加目标追踪; 消退检测中, 吗啡前暴露减少8和60 cm条件下信号追踪而增加60 cm条件下目标追踪。(3)辨别反转学习中, 吗啡前暴露使30和60 cm条件下的大鼠偏爱旧信号、辨别力受损, 减少8、30和60 cm条件下大鼠对新信号的接触。这些结果提示, 距离较少影响吗啡的信号追踪抑制作用和目标追踪增强效应, 而易化吗啡前暴露对反转学习的损害。说明距离是易化成瘾药物对联结学习不利影响而非反转其动机放大作用的重要因素。     

自我和物体为参照系的心理旋转分离：内旋效应

采用虚拟的旋转不同角度左、右手模型,构建“左右手判断(Left and right hand judgment: LR)”任务和“相同－不同判断(same and different judgment: SD)”任务,考察这两种实验任务是否都存在内旋效应和角度效应,以此推论被试采用何种旋转策略。结果发现：（1） 两种实验任务结果均表现出显著的角度效应。（2）在LR任务条件下,存在显著的内旋效应,而在SD任务中不存在内旋效应。从而表明当人手图片作为心理旋转材料时,它具有双重角色。被试心理旋转加工时究竟选用何种参照系的旋转策略,与实验材料和实验任务两者都密不可分     

伏隔核和中脑腹侧被盖区内食欲素在吗啡奖赏中的作用

实验采用条件性位置偏爱（CPP）模型考察中脑腹侧被盖区（VTA）和伏隔核壳区（NAcSh）内食欲素（orexin）在吗啡奖赏中的作用。Wistar大鼠分为盐水训练组和吗啡训练组。3轮吗啡（或盐水）匹配训练前,双侧VTA或NAcSh内给予OXR1拮抗剂SB334867（VTA: 0, 1, 5μg;NAcSh: 0, 1, 3μg）;或2轮吗啡（或盐水）匹配训练前NAcSh内给予orexin A（0, 2, 4, 6μg）,观察其对吗啡CPP建立的影响。结果表明,VTA内给予SB334867抑制吗啡CPP建立,并存在剂量效应关系;NAcSh内给予SB334867或orexin A均未影响吗啡CPP建立,而orexin A可增加吗啡处理大鼠的运动性。以上结果表明,VTA和NAcSh内的orexin在吗啡奖赏中扮演的角色不同,可能调控成瘾行为的不同成分     

不同注意条件下大数与小数的加工差异

考察在注意（注视点）与非注意（非注视点）条件下数字加工的距离效应和符号效应。采用小数（1－4）和大数（6－9）的中文与阿拉伯数字为材料,以判断数字是否大于5为任务。实验结果表明：⑴ 在注意条件下,大小数都出现了距离效应;而在非注意条件下,只有小数出现距离效应;⑵ 在注意条件下,大小数都没有出现符号效应;而在非注意条件下,只有小数出现符号效应,中文数字绩效显著好于阿拉伯数字。     

Conditioned increases in locomotor activity produced with morphine as an unconditioned stimulus, and the relation of conditioning to acute morphine effect and tolerance

Rats administered 5 mg/kg morphine SO4, through subcutaneously implanted catheters, during each of several daily sessions in an open field showed a progressive increase in locomotor activity measured in the open field prior to each morphine administration. Since the increases in activity were not observed in rats given morphine in a different environment (home cage) and saline in the open field, it is concluded that the increases were due to conditioning. In addition, the increases in activity were retained over a 7-day rest period; they were also produced when a second opiate (5 microgram/kg etorphine HCl) was substituted for morphine, were not seen when 2 mg/kg naloxone HCl (ip) was administered during treatment, and were present in rats showing tolerance to opiate-produced hypoactivity. Morphine's direct effect on activity is believed to have a biphasic dose-response curve; therefore, the relation of dose to conditioning was also studied. Increases in activity were the only conditioned behaviors observed; they were present only at the higher doses (16, 4, and 1 vs. .25, .065, and 0 mg/kg), and they occurred whether or not the dose was associated with unconditioned hypoactivity. The discussion deals with the relation of conditioning and morphine tolerance, the question of whether the unconditioned stimulus of morphine conditioning is a compensatory or a direct effect of morphine, and the similarity of conditioned increases in activity produced by morphine and by other stimuli that are reinforcing.     

The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response

We designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.     

Pavlovian Conditioning to a Diazepam Cue with Yohimbine as the Unconditional Stimulus

On multiple occasions, rats were administered diazepam (2.0 mg/kg, ip) followed 30 min thereafter by yohimbine hydrochloride (2.5 or 5.0 mg/kg) or isotonic saline (forward conditioning groups). Three additional groups (backward conditioning controls) were given equivalent injections, but in reverse order. After eight such pairings, the effects of a single injection of diazepam on motor performance (balancing on a rotating drum) was assessed. Rats that had received either dose of yohimbine during forward conditioning trials maintained their balance longer than the saline controls. After four additional conditioning trials, the animals’ activity patterns in a plus-maze screening test for anxiolytics were examined. Placed into the maze after a single test injection of isotonic saline, the behavior of all groups was virtually identical: less than 16% of total entries into or time spent in the four arms of the maze was spent in the two “open” arms (unprotected by surrounding walls). When tested in the maze again, but 35 min after a single injection of diazepam, the groups that had received diazepam but not yohimbine during the conditioning phase exhibited the expected increase in open-arm activity, and equivalent increases were found in backward conditioning groups. However, the group previously conditioned with 2.5 mg/kg of yohimbine following diazepam also showed an increased open-arm activity when tested with diazepam alone, but it was significantly greater than that seen in the control group. In contrast, the group conditioned with 5.0 mg/kg yohimbine following diazepam exhibited no effect of diazepam upon their plus maze activity; consequently, these animals spent less time in the open arms than either of the other groups. Yohimbine alone normally decreases open-arm activity (a putative “anxiogenic” effect) in a linear dose-dependent fashion. The fact that it had a bidirectional conditional effect on the diazepam cue drug demonstrates that a conditional response in drug → drug conditioning cannot always be predicted on the basis of the behavioral response to the signaled drug. Consideration is given to possible reasons for these effects of diazepam → yohimbine pairings in terms of the known neuropharmacological properties of yohimbine.