Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland.
Neuropharmacology. 2010 Jun;58(7):1140-6. doi: 10.1016/j.neuropharm.2010.02.006. Epub 2010 Feb 11.
A pronounced withdrawal syndrome including depressed mood prevents cigarette smoking cessation. We tested if blockade or activation of serotonin (5-HT)(2) receptors affected the time of immobility (as an indirect measure of depression-like behavior) in naïve animals and in those withdrawn from chronic nicotine in the forced swim test (FST). The antidepressant imipramine was used as a control. In the FST, the selective 5-HT(2A) receptor antagonist M100,907 (1-2 mg/kg, but not 0.5 mg/kg), the selective 5-HT(2C) receptor antagonist SB 242,084 (0.3-1 mg/kg, but not 0.1 mg/kg), the 5-HT(2C) receptor agonists Ro 60-0175 (10 mg/kg, but not 3 mg/kg) and WAY 163,909 (1.5-10 mg/kg, but not 0.75 mg/kg) as well as imipramine (30 mg/kg, but not 15 mg/kg) decreased the immobility time while the non-selective 5-HT(2) receptor agonist DOI (0.1-1 mg/kg) was inactive in naïve rats. We found an increase in immobility time in rats that were withdrawn from nicotine exposure after 5 days of chronic nicotine treatment. This effect increased from day 1 until day 10 following withdrawal of nicotine, with maximal withdrawal effects on day 3. M100,907 (1 mg/kg), SB 242,084 (0.3 mg/kg), Ro 60-0175 (3 mg/kg), WAY 163,909 (0.75-1.5 mg/kg) and imipramine (15-30 mg/kg) shortened the immobility time in rats that had been removed from nicotine exposure for 3 days. Locomotor activity studies indicated that the effects of SB 242,084 might have been non-specific, as we noticed enhanced basal locomotion in naïve rats. This data set demonstrates that 5-HT(2A) receptor antagonist and 5-HT(2C) receptor agonists exhibited effects similar to antidepressant drugs and abolished the depression-like effects in nicotine-withdrawn rats. These drugs should be considered as adjuncts to smoking cessation therapy, to ameliorate abstinence-induced depressive symptoms.
明显的戒断综合征，包括抑郁情绪，会阻止戒烟。我们测试了 5-羟色胺（5-HT）（2）受体的阻断或激活是否会影响在强迫游泳试验（FST）中从慢性尼古丁戒断的动物和未经处理的动物的不动时间（作为抑郁样行为的间接测量）。抗抑郁药丙咪嗪被用作对照。在 FST 中，选择性 5-HT（2A）受体拮抗剂 M100907（1-2mg/kg，但 0.5mg/kg 无效）、选择性 5-HT（2C）受体拮抗剂 SB242084（0.3-1mg/kg，但 0.1mg/kg 无效）、5-HT（2C）受体激动剂 Ro60-0175（10mg/kg，但 3mg/kg 无效）和 WAY163909（1.5-10mg/kg，但 0.75mg/kg 无效）以及丙咪嗪（30mg/kg，但 15mg/kg 无效）降低了不动时间，而非选择性 5-HT（2）受体激动剂 DOI（0.1-1mg/kg）在未处理的大鼠中无效。我们发现，在经过 5 天的慢性尼古丁处理后，从尼古丁暴露中戒断的大鼠的不动时间增加。这种效应从戒断后第 1 天持续到第 10 天，第 3 天达到最大戒断效应。M100907（1mg/kg）、SB242084（0.3mg/kg）、Ro60-0175（3mg/kg）、WAY163909（0.75-1.5mg/kg）和丙咪嗪（15-30mg/kg）缩短了从尼古丁暴露中戒断 3 天的大鼠的不动时间。运动活性研究表明，SB242084 的作用可能是非特异性的，因为我们注意到在未处理的大鼠中基础运动增强。这个数据集表明，5-HT（2A）受体拮抗剂和 5-HT（2C）受体激动剂表现出与抗抑郁药物相似的作用，并消除了尼古丁戒断大鼠的抑郁样效应。这些药物应被视为戒烟治疗的辅助手段，以改善戒断引起的抑郁症状。
