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Nicotine chronic tolerance development and withdrawal in the planaria (Schmidtea mediterranea)
Pharmacology Biochemistry and Behavior ( IF 3.3 ) Pub Date : 2020-11-24 , DOI: 10.1016/j.pbb.2020.173075
Fatih Sal , Jose Prados , Gonzalo P. Urcelay

Chronic nicotine exposure reduces sensitivity to the effects of nicotine, which then results in behavioural changes and tolerance development. In the planaria, a valuable first-stage preclinical model for addictive behaviour, acute nicotine administration has been shown to steadily alter the motility of the animals, a result that has been interpreted as evidence of tolerance and withdrawal effects; however, chronic exposure - typically regarded as a condition for the development of tolerance - and the role of the contextual cues have not been systematically assessed. The present study assessed the acute and chronic effects of nicotine on the motility of planarians (Schmidtea mediterranea). The animals in the experimental groups received long chronic exposure to nicotine (ten daily 30 min exposures); a control group was exposed to water in the same context but in the absence of the drug. The motility of the animals was closely monitored on every exposure. Following this phase, all the animals were subject to three different tests: in the presence of the exposure context (without the drug, Test 1); in the presence of nicotine in the exposure context (Test 2); and in the presence of the drug in a novel context (Test 3). Exposure to nicotine consistently reduced motility; the motility in the presence of nicotine increased with repeated exposures to the drug, an instance of tolerance development. Tolerance development was dependent on nicotinic receptor activation, because it was blocked by the co-administration of mecamylamine. However, this tolerance was found to be independent of the contextual cues where the effects of the drug had been experienced. The results are discussed by reference to the existent theories of tolerance development to drugs.



中文翻译:

尼古丁慢性耐受的发展和戒断的退缩(Schmidtea mediterranea

慢性尼古丁暴露降低了对尼古丁作用的敏感性,继而导致行为改变和耐受性发展。在涡虫中,一种令人上瘾的有价值的第一阶段临床前临床模型-急性尼古丁给药已显示出稳定地改变动物的运动能力,这一结果已被解释为耐受和戒断作用的证据。但是,长期暴露-通常被认为是产生耐受性的条件-以及上下文提示的作用尚未得到系统的评估。本研究评估了尼古丁对涡虫(Schmidtea mediterranea)运动的急性和慢性影响)。实验组中的动物长期长期暴露于尼古丁(每天十次,每次30分钟)。对照组在相同背景下但没有药物的情况下暴露于水。在每次暴露时都密切监测动物的运动能力。在此阶段之后,对所有动物进行三种不同的测试:在暴露环境下(无药物,测试1);在暴露环境中存在尼古丁时(测试2);并在新环境中使用该药物(测试3)。接触尼古丁会持续降低运动能力;尼古丁存在下的运动性随着反复接触药物而增加,这是耐受性发展的一个实例。耐受性的发展取决于烟碱样受体的激活,因为它被美卡明胺的共同给药所阻断。然而,发现这种耐受性与经历药物作用的上下文线索无关。通过参考现有的药物耐受性发展理论来讨论结果。

更新日期:2020-12-04
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