Biała Grażyna, Polak Piotr, Michalak Agnieszka, Kruk-Słomka Marta, Budzyńska Barbara
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
Pharmacol Rep. 2014 Apr;66(2):212-22. doi: 10.1016/j.pharep.2014.02.003. Epub 2014 Mar 3.
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.
Mice were chronically treated with nicotine (seven days, three times daily, 3.35 mg/kg, sc) or D-amphetamine (14 days, once daily, 2.5mg/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.
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 20mg/kg, ip), injected before the test, attenuated above-mentioned signs of drug withdrawal.
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.
精神兴奋剂戒断的非躯体症状在动物模型中难以体现，但在人类中似乎会促使药物寻求和复吸；因此，了解介导此类行为的机制很重要。本研究旨在探讨尼古丁和D-苯丙胺急性及长期戒断时，与负性非躯体及快感缺失相关症状的钙依赖机制。
小鼠分别接受尼古丁（7天，每日3次，3.35mg/kg，皮下注射）或D-苯丙胺（14天，每日1次，2.5mg/kg，腹腔注射）的长期治疗。然后，在戒断的第1天、第7天或第14天，研究焦虑或抑郁相关效应以及认知或痛觉感受。
我们的结果表明，分别在D-苯丙胺或尼古丁戒断的第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，主要发现表明，在测试前注射钙通道拮抗剂，即尼莫地平、维拉帕米和氟桂利嗪（10和20mg/kg，腹腔注射），可减轻上述药物戒断症状。
因此，这些发现支持了这样的假设，即类似的钙依赖机制参与了与尼古丁或D-苯丙胺戒断相关的厌恶非躯体成分。我们可以认为钙通道阻滞剂有减轻药物戒断的潜力，因此可能作为药物戒断和复吸的药物治疗有益。
