Irvine E E, Cheeta S, File S E
Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, SE1 1UL, London, UK.
Pharmacol Biochem Behav. 2001 Feb;68(2):319-25. doi: 10.1016/s0091-3057(00)00449-4.
In the elevated plus-maze test of anxiety, nicotine (0.1 mg/kg sc; 30 min after injection) had a significant anxiogenic effect, shown by specific decreases in the percentage of time spent on the open arms and in the percentage of open-arm entries. Tolerance developed to this anxiogenic effect after 7 days of nicotine treatment (0.1 mg/kg/day). Five minutes after an acute injection, nicotine (0.1 mg/kg) was ineffective, but after 7 days of treatment a significant anxiolytic effect, shown by specific increases in the percentage of time spent on the open arms and in the percentage of open-arm entries, emerged. After 14 days of nicotine treatment, tolerance developed to this anxiolytic effect. There was a complete dissociation between the effects of nicotine on the measures of anxiety, and on the locomotor activity as measured by closed-arm entries. No changes in closed-arm entries were found after acute administration of nicotine, but rats tested 30 min after their 7th injection made significantly fewer, and those tested 5 min after their 14th injection made significantly more, entries than their respective controls. Rats that were tested after 24 h withdrawal from six daily nicotine injections showed a significant anxiogenic effect. A low dose of nicotine (5 ng) injected into the dorsal hippocampus was without effect in vehicle pretreated rats, but it was able to reverse the anxiogenic effect found after 24 h of withdrawal from 6 days of nicotine treatment.
在焦虑的高架十字迷宫试验中，尼古丁（皮下注射0.1mg/kg；注射后30分钟）具有显著的致焦虑作用，表现为在开放臂上停留时间的百分比和进入开放臂次数的百分比特异性降低。尼古丁治疗7天（0.1mg/kg/天）后，对这种致焦虑作用产生了耐受性。急性注射后5分钟，尼古丁（0.1mg/kg）无效，但治疗7天后出现了显著的抗焦虑作用，表现为在开放臂上停留时间的百分比和进入开放臂次数的百分比特异性增加。尼古丁治疗14天后，对这种抗焦虑作用产生了耐受性。尼古丁对焦虑测量指标的影响与对通过封闭臂进入次数测量的运动活动的影响完全分离。急性给予尼古丁后，封闭臂进入次数没有变化，但在第7次注射后30分钟测试的大鼠进入次数明显减少，在第14次注射后5分钟测试的大鼠进入次数明显多于各自的对照组。在每天注射6次尼古丁后停药24小时进行测试的大鼠表现出显著的致焦虑作用。向经载体预处理的大鼠海马背侧注射低剂量尼古丁（5ng）无效，但它能够逆转在6天尼古丁治疗停药24小时后发现的致焦虑作用。
