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The place conditioning paradigm was used to assess the ability of the noncompetitive NMDA receptor antagonist, MK-801, to interfere with drug-place associations. MK-801 (0.1 mg/kg, i.p.) attenuated a place preference produced by high, but not low to moderate, doses of amphetamine. Interference with amphetamine place preference learning was not the result of state-dependent retrieval produced by MK-801. Furthermore, MK-801 did not interfere with the expression of a previously established amphetamine place preference. Pretreatment with MK-801 also interfered with lithium-induced conditioned place aversion learning. These results suggest that the attenuation of place preference conditioning produced by MK-801 is the result of its interference with learning rather than with the rewarding properties of drugs. 相似文献
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The effect of morphine preexposure on place conditioning with morphine was investigated. In the first experiment, five injections of 10 mg/kg morphine were administered to rats prior to place conditioning or taste-aversion training with morphine. Although this number of preexposures retarded taste-aversion learning, there was no effect on place conditioning. In subsequent experiments we investigated the role of context blocking in UCS preexposure in place conditioning. In one experiment, preexposure to five morphine injections prior to place conditioning resulted in a reduced place preference, compared with preexposure and place conditioning in different contexts. However, the overall detrimental effect of morphine preexposure was questionable, because the rats that were preexposed were only marginally different from those that were not preexposed. In a final experiment we examined the effect of a context change from preexposure to place conditioning with 15 preexposures and demonstrated a detrimental effect of preexposure on place conditioning that was context specific. These results support a role of classical conditioning in place-preference conditioning with morphine. 相似文献
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Drugs of abuse have been reported to produce both rewarding and aversive effects, as evidenced by their ability to induce
both conditioned place preferences (CPPs) and conditioned taste aversions (CTAs), respectively. Although several attempts
have been made to assess the relationship between the rewarding and aversive effects of drugs in independent groups, it is
unknown to what extent (if any) preferences and aversions are related in individual animals. The present study assessed this
relationship by examining the ability of morphine (5 and 10 mg/kg) and amphetamine (3 and 5 mg/kg) to induce both place preferences
and taste aversions in the same animal, using a concurrent CTA/CPP design. There was no consistent relationship between the
ability of morphine or amphetamine at either dose to increase time spent on the drug-paired side and the ability to suppress
consumption of the drug-paired taste. These results support the position that drugs of abuse have multiple stimulus effects,
both rewarding and aversive, that condition place preferences and taste aversions independently. 相似文献
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The present experiments were designed to determine the effect of conditioning trial duration on strength of ethanol-induced conditioned place preference in mice. In a counterbalanced, differential conditioning procedure, DBAI2J mice received four pairings of a distinctive tactile (floor) stimulus with injection of ethanol (2 g/kg); a different floor stimulus was paired with saline. Different groups were exposed to the floor stimuli for 5, 15, or 30 min after injection. Conditioned place preference was inversely related to trial duration, with mice in the 5-, 15-, and 30-mmn groups, spending 83%, 74%, and 66% of their time, respectively, on the ethanol-paired floor during a choice test. This outcome was replicated in a second experiment, which also showed that context familiarity can influence conditioned place preference. In general, these findings suggest that ethanol’s rewarding effect is greatest shortly after injection. 相似文献
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Sheng-hong ZHU ;Li-jia ZHOU ;Hong JIANG ;Rong-jun CHEN ;Chuan LIN ;Shi FENG ;Juan JIN ;Jiang-hua CHEN ;Jian-yong WU 《Journal of Zhejiang University. Science. B》2014,15(8):735-742
研究目的:在小鼠模型中利用吲哚美辛阻断COX-1/2通路,探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。创新要点:非甾体类抗炎药被认为具有肾毒性,本研究首次在小鼠模型中探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。研究方法:小鼠左侧肾蒂夹闭后,通过腹腔注射不同剂量的吲哚美辛,在肾缺血再灌注损伤24小时后,获取血液和肾脏标本。利用酶联免疫(ELISA)试剂盒测定血清肌酐和细胞因子浓度来评估肾功能,肾组织样本进行苏木精-伊红染色和免疫组化分析。重要结论:腹腔注射吲哚美辛5 mg/kg组的小鼠血清肌酐值与对照组相比显著降低,肾小管损伤也显著减轻(见图1和2);腹腔注射5和7 mg/kg吲哚美辛组的小鼠血清肾肿瘤坏死因子-α和白介素-6的浓度显著降低(见图3a和3b);腹腔注射3和5 mg/kg吲哚美辛组的小鼠血清血栓素B2与6-酮前列腺素F1α的比值明显降低(见图3c);腹腔注射5 mg/kg吲哚美辛组小鼠肾组织COX-1和COX-2染色较弱(见图4)。因此,吲哚美辛对小鼠肾缺血再灌注损伤的作用与其剂量相关,在某个特定的剂量范围内具有肾保护作用。吲哚美辛对小鼠肾缺血再灌注损伤的保护作用与阻断COX-1/2有关。 相似文献
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In Experiment 1, the amount of time rats spent engaged in a range of behaviors was recorded immediately prior to and following the intraperitoneal administration of morphine sulfate (6 mg/kg) or distilled water. No behavioral differences were observed between these groups. In Experiment 2, preexposure to this low dose of morphine attenuated the subsequent acquisition of a morphine-induced taste aversion independent of the similarity of the preexposure and conditioning environments. These results with a dose of morphine that does not produce any behavioral effects, which in turn could potentially mask associative conditioning during preexposure, confirm that the attenuating effects of morphine preexposure on taste aversion learning are nonassociative. 相似文献
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Chronic morphine drinking establishes morphine tolerance, but not addiction in Wistar rats 总被引：1，自引：0，他引：1
Binsack R Zheng ML Zhang ZS Yang L Zhu YP 《Journal of Zhejiang University. Science. B》2006,7(11):892-898
Objective： Some animal models apply morphine in the drinking water to generate addiction, but related reports are not free of conflicting results. Accordingly, this study aimed to figure out if chronic consumption of morphine in the drinking water can induce morphine addiction in Wistar rats. Methods： For 3 weeks, the animals received a daily morphine dose of 35 mg/kg by offering a calculated volume of sugar water （5% sucrose） with morphine （0. l mg/ml） to each rat; animals receiving just sugar water served as controls. Immediately after the treatment phase, the tail immersion test was used to check for morphine tolerance, and all animals were then kept on tap water for one week （withdrawal phase）. Afterwards, all rats were allowed to choose their drinking source by offering two bottles, containing sugar water without and with morphine, simultaneously for two days （preference phase）. Results： While the chronic consumption of morphine led to a reduction in body weight and to morphine tolerance, the morphine-treated Wistar rats did not show any preference for the opiate-containing sugar water. Conclusion： Body weight loss and tolerance do not reveal a condition of drug craving, and current animal models should be re-evaluated regarding their potential to establish morphine addicted animals. 相似文献
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Pentobarbital is self-administered by rats but has also been reported to produce a conditioned place aversion. Since the self-administration and place preference paradigms both are considered to assess drug reward, we further examined the hedonic properties of pentobarbital, using place conditioning. In Experiment 1, a dose of 15 mg/kg (intraperitoneal) of pentobarbital produced a conditioned place aversion after 4 conditioning trials of various durations (5, 15, 30, or 60 min). Since rats are typically drug experienced in the self-administration paradigm, in Experiments 2 and 3, we examined the effect of drug history on pentobarbital-induced place conditioning. Although preexposure to pentobarbital attenuated the place aversion, it never resulted in a place preference. As has been reported with alcohol, pentobarbital is hedonically aversive in rats, when novel. 相似文献
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Christopher L. Cunningham Dobrina M. Okorn Christine E. Howard 《Learning & behavior》1997,25(1):31-42
DBA/2J mice were exposed to a distinctive floor stimulus (CS+) and ethanol (2 g/kg) in a place conditioning paradigm. A different floor stimulus (CS?) was presented with saline. Mice injected just before or 30 min before CS exposure (Groups 0, ?30) showed conditioned place preference, whereas mice injected right after exposure to the CS (Group 5) displayed place aversion (Experiment 1). None of the other groups (?120, ?60, 15, 60) showed place conditioning. Handling and saline injection given just before or after CS exposure were unable to produce place conditioning (Experiment 2). However, there was a positive relationship between ethanol concentration (10% vs. 20%) and test performance, suggesting that peritoneal irritation influences place conditioning (Experiment 3). Overall, these findings support the suggestion that intraperitoneal injection of ethanol produces an initial short-duration aversive effect that is followed by a longer lasting positive motivational effect. 相似文献
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苦参总碱抗心律失常作用的实验研究 总被引：6，自引：0，他引：6
苦参总碱（Tital Alkaloid of Sophora Flavescens,TASF）20mg/kg,40mg/kg能明显对抗鸟头碱20ug/kg,BaCl2 2mg/kg和结扎左冠状动脉前降支诱发大鼠的室性心律失常.TASF也能明显对抗CaCl2-Ach（CaCl20.6％+Ach 0.0025％）混合液10ml/kg诱发小鼠心房纤颤或扑动.大鼠心电图（ECG）试验证明TASF有负性频率作用,负性传导作用.这些作用可能是TASF抗心律失常作用的药理学基础. 相似文献
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The growth inhibitory effects of D-glucosamine hydrochloride （GlcNH2-HCl）, D-glucosamine （GlcNH2） and N-acetyl glucosamine （NAG） on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH2.HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT （3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide） assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH2-HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells. GlcNH2-HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125-500 mg/kg, dose of 250 mg/kg being the best. GlcNH2-HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH2-HCl is probably host-mediated and cytocidal. 相似文献
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观察N-甲基-D天冬氨酸（N-methyl-D-aspartic acid receptor,NMDA）受体拮抗剂美金刚对小鼠条件性恐惧记忆的影响.将小鼠随机分成生理盐水组、美金刚低剂量组、美金刚高剂量组.通过三种不同的给药时间和测试方法来检测不同情况下小鼠的僵直度.结果表明,急性药物预处理过程中,不同剂量的美金刚对小鼠的短期和长期记忆有不同的影响,而药物对小鼠恐惧记忆的消退没有显著作用.由此可见,美金刚对小鼠的条件恐惧记忆能够产生一定的作用,此作用随药物浓度和药物处理方式的不同而改变. 相似文献
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Drugs of abuse have both rewarding and aversive effects, as indexed by the fact that they support place preferences and taste aversions, respectively. In the present study, we explored whether having a history with the aversive effects of morphine (via taste aversion conditioning) impacted the subsequent rewarding effects of morphine, as measured in the place preference design. In Experiment 1, rats were exposed to a taste aversion procedure in which saccharin was followed by morphine. Place preference conditioning was then initiated in which animals were injected with morphine and placed on one side of a two-chambered apparatus. Animals with a taste aversion history acquired place preferences to the same degree as controls without such a history, suggesting that morphine’s affective properties condition multiple effects, dependent on the specific stimuli present during conditioning. To determine whether these results were a reflection of processes operating in traditional associative conditioning, in a modified blocking procedure, place preference conditioning was attempted in the presence of a taste previously associated with morphine (Exp. 2). Under these conditions, animals still acquired morphine-induced place preferences comparable to those of animals without a morphine or conditioning history. These results are consistent with the position that drugs of abuse have multiple stimulus effects (positive and negative) that are differentially associated with specific stimuli (environmental and taste) that drive different behavioral responses (approach and avoidance). 相似文献
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探讨PFOS对雄性小鼠睾丸细胞凋亡以及相关基因表达的影响。40只雄性昆明系小鼠随机分成PFOS 0、1.25、2.5、5.0和10.0 mg/kg,共5组,通过饮水方法染毒35天。处死小鼠,取睾丸,流式细胞仪观察细胞凋亡RT-PCR观察Bax和Bcl-2基因表达。细胞凋亡率随着PFOS的浓度增加而增加,各剂量组与对照组比较均有显著性差异;10mg/kg/d PFOS实验组小鼠睾丸组织中Bax基因表达与对照组比较显著上升(p<0.05),其他剂量组变化与对照组比较差异无统计学意义(p>0.05)。随着染毒剂量的增加,Bcl-2基因表达下降,5.0、10.0 mg/kg/d PFOS实验组与对照组相比差异有统计学意义(分别为p<0.05,p<0.01)PFOS能够引起睾丸细胞凋亡增加,Bax和Bcl基因表达改变可能是其机制之一。 相似文献
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何凤琴 《西安文理学院学报》2009,12(4):1-5
为了验证雷公藤混合饵料和莪术葡萄糖注射液的混合饵料对农田害鼠的防治效果,在种植小麦的农田中进行了大面积的实验.实验结果表明害鼠对0.3 mg/kg雷公藤混合饵料、30 mg/kg莪术葡萄糖注射液混合饵料及0.3 mg/kg雷公藤和30 mg/kg莪术葡萄糖注射液的混合饵料的适口性没有显著性差异;3种混合饵料发挥作用后,害鼠数量明显少于混合饵料发挥作用前,实验结果进一步表明：3种混合饵料均可以作为环保型鼠药加以推广应用.由于30 mg/kg莪术葡萄糖注射液混合饵料实验产品成本最低,可以重点推荐使用. 相似文献
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Tolerance to morphine-induced hypoactivity in hamsters was investigated under conditions designed to test a Pavlovian conditioning model of morphine tolerance. One group of animals received i.p. injections of morphine (50 mg/kg) in the test environment and saline in the home cage; a second group received saline in the test environment and morphine in the home cage; a third group received saline in both environments. A subsequent morphine challenge in the test environment gave evidence of both associative and nonassociative tolerance. Associative tolerance was detectable 1 week later during a second morphine challenge. Compensatory hyperactivity, however, was not observed during a saline challenge in the presence of morphine-associated cues. Following the acquisition of tolerance, nonreinforced exposure to morphine-associated cues produced an attenuation of morphine tolerance (i.e., extinction of tolerance). The results are interpreted as providing partial support for the Pavlovian model and are discussed in terms of alternative associative models of tolerance. 相似文献
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