Influence of calcium channel antagonists on nonsomatic signs of nicotine and D-amphetamine withdrawal in mice
Influence of calcium channel antagonists on nonsomatic signs of nicotine and D-amphetamine withdrawal in mice
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DOI：
10.1016/j.pharep.2014.02.003
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发表时间：
2014-04-01
影响因子：
4.4
通讯作者：
Budzynska, Barbara
中科院分区：
文献类型：
--
作者：
Biala, Grazyna;Polak, Piotr;Budzynska, Barbara
背景：精神兴奋剂戒断的非躯体症状，难以在动物模型中证明，可能会促进人类的药物寻求和药物复发；因此，理解调解这类行为的机制是很重要的。本研究旨在探讨急性和长期戒断尼古丁和d -安非他明的阴性非躯体和快感缺乏相关症状的钙依赖机制。方法：小鼠长期服用尼古丁（7天，每日3次，3.35 mg/kg, sc）或d -安非他明（14天，每日1次，2.5 mg/kg, ip）。然后，在戒断的第一天、第7天或第14天，研究焦虑或抑郁相关的影响，以及认知或伤害感受。结果：我们的研究结果表明，分别在d -安非他明或尼古丁戒断的第7天或第14天，小鼠表现出焦虑和抑郁样效应增加，记忆障碍和痛觉过敏。此外，主要研究结果表明，在试验前注射钙通道拮抗剂，即尼莫地平、维拉帕米和氟桂嗪（10和20 mg/kg， ip），可减轻上述药物戒断迹象。结论：作为结果，这些发现支持了一种假设，即类似的钙依赖机制涉及与尼古丁或d -安非他明戒断相关的令人厌恶的非躯体成分。我们可以建议钙通道阻滞剂有可能减轻药物戒断，因此可能有利于药物停止和复发的药物治疗。(C) 2014年波兰科学院药理学研究所。Elsevier Urban & Partner Sp. z . oo出版，版权所有。
Background: Nonsomatic signs of psychostimulant withdrawal, difficult to demonstrate in animal paradigms, may appear to promote drug seeking and drug relapse in humans; thus, it is important to understand the mechanisms that mediate this kind of behaviors. The present study was undertaken to examine the calcium-dependent mechanism of negative nonsomatic and anhedonia-related symptoms of acute and protracted withdrawal of nicotine and D-amphetamine.Methods: Mice were chronically treated with nicotine (seven days, three times daily, 3.35 mg/kg, sc) or D-amphetamine (14 days, once daily, 2.5 mg/kg, ip). Then, at the first, seventh or 14th day of withdrawal, anxiety- or depression-related effects, as well as cognition or nociception were studied.Results: Our results demonstrated that, at the seventh or 14th day of D-amphetamine or nicotine withdrawal, respectively, mice exhibited increased anxiety and depression-like effects, memory impairment and hyperalgesia. Further, major findings showed that calcium channel antagonists, i.e., nimodipine, verapamil and flunarizine (10 and 20 mg/kg, ip), injected before the test, attenuated above-mentioned signs of drug withdrawal.Conclusions: As an outcome, these findings support the hypothesis that similar calcium-dependent mechanisms are involved in an aversive nonsomatic component, associated with nicotine or D-amphetamine withdrawal. We can suggest that calcium channel blockers have potential to alleviate drug withdrawal and may thus be beneficial as pharmacotherapy of drug cessation and relapse. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.