Biala Grazyna, Kruk Marta
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.
J Pharm Pharmacol. 2009 Apr;61(4):493-502. doi: 10.1211/jpp/61.04.0012.
A variety of abused drugs, including psychostimulants, can modulate the expression of anxiety. Although the effect of nicotine and D-amphetamine on anxiety-related behaviour in animal models has been investigated, the mechanisms underlying the anxiogenic or anxiolytic actions of these drugs have not been clarified. Bupropion is an antidepressant drug which may alleviate some symptoms of nicotine withdrawal, although its effects on anxiety are not clear. We have investigated the effect of nicotine and D-amphetamine on anxiety in the elevated plus maze test in mice.
We examined the influence of acute administration of nicotine (0.1 mg/kg, s.c.) and D-amphetamine (2 mg/kg, i.p.) on anxiety level. We then evaluated the anxiety-related response after subchronic injection of both psychostimulants, including crossover effects. For this purpose, nicotine (0.1 mg/kg, s.c.) was administered daily for six days, and on the seventh day mice were challenged with nicotine (0.1 mg/kg, s.c.) or D-amphetamine (2 mg/kg, i.p.). A distinct group of mice was pretreated with D-amphetamine (2 mg/kg, i.p., 8 days), and subjected to D-amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.) challenge on the ninth day. Moreover, we investigated acute and subchronic effects of coadministration of bupropion (5, 10 and 20 mg/kg; i.p.) and nicotine or D-amphetamine.
We observed that acute anxiogenic effects of nicotine and D-amphetamine as well as the development of tolerance and cross-tolerance to their effects were blunted by a pretreatment with a nonactive dose of bupropion (5 mg/kg, i.p.).
These results demonstrated that similar neural mechanisms were involved in the regulation of nicotine and D-amphetamine anxiety-like behaviour in mice. The results have provided new findings to support the use of bupropion in the treatment of nicotine and/or amphetamine addiction.
包括精神兴奋剂在内的多种滥用药物可调节焦虑情绪的表达。尽管已经研究了尼古丁和右旋苯丙胺对动物模型中焦虑相关行为的影响，但这些药物产生致焦虑或抗焦虑作用的潜在机制尚未阐明。安非他酮是一种抗抑郁药物，可能会缓解尼古丁戒断的一些症状，但其对焦虑的影响尚不清楚。我们在小鼠高架十字迷宫试验中研究了尼古丁和右旋苯丙胺对焦虑的影响。
我们检测了急性给予尼古丁（0.1毫克/千克，皮下注射）和右旋苯丙胺（2毫克/千克，腹腔注射）对焦虑水平的影响。然后，我们评估了两种精神兴奋剂亚慢性注射后的焦虑相关反应，包括交叉效应。为此，每天皮下注射尼古丁（0.1毫克/千克），持续六天，在第七天，用尼古丁（0.1毫克/千克，皮下注射）或右旋苯丙胺（2毫克/千克，腹腔注射）对小鼠进行激发试验。另一组不同的小鼠先用右旋苯丙胺（2毫克/千克，腹腔注射，共8天）进行预处理，并在第九天用右旋苯丙胺（2毫克/千克，腹腔注射）或尼古丁（0.1毫克/千克，皮下注射）进行激发试验。此外，我们研究了安非他酮（5、10和20毫克/千克；腹腔注射）与尼古丁或右旋苯丙胺联合给药的急性和亚慢性影响。
我们观察到，用无活性剂量的安非他酮（5毫克/千克，腹腔注射）预处理可减弱尼古丁和右旋苯丙胺的急性致焦虑作用以及对其作用的耐受性和交叉耐受性的形成。
这些结果表明，小鼠中尼古丁和右旋苯丙胺的焦虑样行为调节涉及相似的神经机制。这些结果为支持使用安非他酮治疗尼古丁和/或苯丙胺成瘾提供了新的发现。
