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大鼠对新环境的运动反应性及对阿片类药物敏感性的个体差异。II. 激动剂诱导的抗伤害感受和拮抗剂诱导的液体消耗抑制。

Individual differences in locomotor reactivity to a novel environment and sensitivity to opioid drugs in the rat. II. Agonist-induced antinociception and antagonist-induced suppression of fluid consumption.

作者信息

White David A, Kalinichev Mikhail, Holtzman Stephen G

机构信息

Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, NE, Suite 5074, Atlanta, GA 30322, USA.

出版信息

Psychopharmacology (Berl). 2004 Dec;177(1-2):68-78. doi: 10.1007/s00213-004-1921-8. Epub 2004 Jul 2.

Abstract

RATIONALE

In an animal model for vulnerability to drug abuse, rats that are more reactive to a novel environment (high responders, HRs) are more sensitive to behavioral effects of psychostimulants than are less reactive rats (low responders, LRs). In a companion article, we reported that HRs and LRs differ in sensitivity to morphine-induced locomotor sensitization.

OBJECTIVE

We tested whether LRs and HRs also differ in sensitivity to opioid-induced antinociception and opioid antagonist-induced suppression of fluid consumption.

METHODS

LRs and HRs were categorized based on motor responses to novelty during a 30-min session. Responses to nociceptive stimuli of varied intensities were measured using the tail-flick and hot-plate tests alone or following cumulative doses of morphine (1.0-12 mg/kg), buprenorphine (0.025-0.6 mg/kg), or etorphine (0.25-6.0 microg/kg). Potential changes in endogenous opioid-mediated reward systems were tested using naltrexone-induced (0.01-30 mg/kg) suppression of drinking either water following 24-h deprivation or sweetened condensed milk in a non-deprived state. These effects were further examined following 2 weeks of daily access to sweetened condensed milk.

RESULTS

At the lowest stimulus intensity tested, HRs had significantly shorter tail-flick response latencies than LRs. Additionally, HRs were less responsive to cumulative doses of morphine than LRs. There were no overall group differences in the hot-plate test. Following 2 weeks of daily access to sweetened condensed milk, HRs were more sensitive to naltrexone-induced suppression of consumption.

CONCLUSIONS

Under the proper conditions, differences in sensitivity to opioid drugs between HRs and LRs at least partially extend to antinociceptive and appetitive reward systems and are suggestive of more extensive differences in phenotype. As with the effects of repeated morphine exposure on locomotor activity, the effect of repeated exposure to appetitive reward associated with sweetened milk appears to be more robust in LRs than HRs.

摘要

原理

在药物滥用易感性的动物模型中,对新环境反应更强的大鼠(高反应者,HRs)比反应较弱的大鼠(低反应者,LRs)对精神兴奋剂的行为效应更敏感。在一篇相关文章中,我们报道了HRs和LRs对吗啡诱导的运动敏化的敏感性存在差异。

目的

我们测试了LRs和HRs对阿片类药物诱导的镇痛作用以及阿片类拮抗剂诱导的液体消耗抑制的敏感性是否也存在差异。

方法

根据在30分钟的实验过程中对新环境的运动反应对LRs和HRs进行分类。单独使用甩尾和热板试验或在给予累积剂量的吗啡(1.0 - 12毫克/千克)、丁丙诺啡(0.025 - 0.6毫克/千克)或埃托啡(0.25 - 6.0微克/千克)后测量对不同强度伤害性刺激的反应。使用纳曲酮诱导(0.01 - 30毫克/千克)来测试内源性阿片介导的奖赏系统的潜在变化,即抑制24小时禁水后的饮水或非禁水状态下的甜炼乳饮用。在每天给予甜炼乳2周后进一步检查这些效应。

结果

在测试的最低刺激强度下,HRs的甩尾反应潜伏期明显短于LRs。此外,HRs对吗啡累积剂量的反应比LRs小。在热板试验中没有总体的组间差异。在每天给予甜炼乳2周后,HRs对纳曲酮诱导的消耗抑制更敏感。

结论

在适当条件下,HRs和LRs对阿片类药物敏感性的差异至少部分扩展到镇痛和奖赏系统,提示表型存在更广泛的差异。与重复吗啡暴露对运动活动的影响一样,重复暴露于与甜炼乳相关的奖赏的影响在LRs中似乎比HRs更强。

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