Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland.
Pharmacol Biochem Behav. 2010 Aug;96(2):141-7. doi: 10.1016/j.pbb.2010.04.022. Epub 2010 May 6.
The present study focused on the evaluation of behavioural sensitization and cross-sensitization induced by nicotine and morphine in mice. First, we revealed that after 9days of nicotine administration (0.175mg/kg, free base), every other day and following its 7-day withdrawal, challenge doses of nicotine (0.175mg/kg) and morphine (5mg/kg) induced locomotor sensitization in mice. When we examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist (0.5, 1 and 2mg/kg) and mecamylamine (0.5, 1 and 2mg/kg), a non-selective nicotinic receptor antagonist, we found that both agents attenuated the acquisition and expression of nicotine sensitization as well as locomotor cross-sensitization between nicotine and morphine. Our results indicate similar cholinergic mechanisms involved in the locomotor stimulant effects of nicotine and morphine in mice, and as such these data may suggest that nicotinic neurotransmission could be a potential target for developing pharmacotherapeutic strategies to treat and prevent nicotine and/or opioid addiction.
本研究旨在评估尼古丁和吗啡在小鼠体内诱导的行为敏化和交叉敏化。首先，我们发现，在给予尼古丁（0.175mg/kg，游离碱）9 天后，每隔一天并在其 7 天戒断后，给予尼古丁（0.175mg/kg）和吗啡（5mg/kg）挑战剂量会导致小鼠运动敏化。当我们研究烟碱的部分α4β2 烟碱受体激动剂（0.5、1 和 2mg/kg）和美加明（0.5、1 和 2mg/kg），一种非选择性烟碱受体拮抗剂的影响时，我们发现这两种药物都能减弱尼古丁敏化的获得和表达，以及尼古丁和吗啡之间的运动交叉敏化。我们的结果表明，在小鼠中，尼古丁和吗啡的运动兴奋剂作用涉及相似的胆碱能机制，因此这些数据可能表明烟碱能神经传递可能是开发治疗和预防尼古丁和/或阿片成瘾的药物治疗策略的潜在靶点。
