Zaniewska Magdalena, McCreary Andrew C, Stefański Roman, Przegaliński Edmund, Filip Małgorzata
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland.
Synapse. 2008 Dec;62(12):935-9. doi: 10.1002/syn.20564.
The objective of this study was to evaluate the efficacy of varenicline, a novel partial agonist at alpha 4 beta 2 and full agonist at alpha 7 nicotinic acetylcholine receptor (nAChR) subtypes, in blocking the locomotor effects of acute or repeated treatments with nicotine (0.4 mg/kg, s.c.) in rats. Varenicline (0.3-3 mg/kg, s.c.) by itself enhanced the basal locomotor activity in naive rats while it had an inhibitory effect on acute nicotine-induced hyperlocomotion. Varenicline (0.3-3 mg/kg) did not change the nicotine-evoked conditioned locomotion, but when administered to nicotine-sensitized rats (0.1 and 1 mg/kg), reduced the expression of nicotine sensitization. In another set of experiments, varenicline (1 mg/kg) administered during the second withdrawal period (days 11-14) to nicotine-treated rats, attenuated the reestablishment of the expression of nicotine sensitization. Our pharmacological analyses further support the hypothesis that varenicline might be a useful treatment for smoking cessation considering its actions on the locomotor and reinforcing effects of nicotine without inhibition of conditioned locomotion.
本研究的目的是评估伐尼克兰（一种新型的α4β2亚型烟碱型乙酰胆碱受体（nAChR）的部分激动剂和α7亚型的完全激动剂）对阻断尼古丁（0.4mg/kg，皮下注射）急性或重复给药对大鼠运动效应的效果。伐尼克兰（0.3 - 3mg/kg，皮下注射）单独使用时可增强未接触过尼古丁的大鼠的基础运动活性，同时对急性尼古丁诱导的运动亢进有抑制作用。伐尼克兰（0.3 - 3mg/kg）不改变尼古丁诱发的条件性运动，但给予尼古丁致敏大鼠（0.1和1mg/kg）时，可降低尼古丁致敏的表达。在另一组实验中，在尼古丁处理大鼠的第二个戒断期（第11 - 14天）给予伐尼克兰（1mg/kg），可减弱尼古丁致敏表达的重新建立。我们的药理学分析进一步支持了这样的假设，即考虑到伐尼克兰对尼古丁运动和强化效应的作用而不抑制条件性运动，它可能是一种有效的戒烟治疗药物。
