Hashemizadeh Shiva, Sardari Maryam, Rezayof Ameneh
Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jun 3;51:65-71. doi: 10.1016/j.pnpbp.2014.01.010. Epub 2014 Jan 24.
In the present study, the effects of bilateral microinjections of cannabinoid CB1 receptor agonist and antagonist into the basolateral amygdala (intra-BLA) on nicotine-induced place preference were examined in rats. A conditioned place preference (CPP) apparatus was used for the assessment of rewarding effects of the drugs in adult male Wistar rats. Subcutaneous (s.c.) administration of nicotine (0.2mg/kg) induced a significant CPP, without any effect on the locomotor activity during the testing phase. Intra-BLA microinjection of a non-selective cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (0.1-0.5 μg/rat) with an ineffective dose of nicotine (0.1mg/kg, s.c.) induced a significant place preference. On the other hand, intra-BLA administration of AM251 (20-60 ng/rat), a selective cannabinoid CB1 receptor antagonist inhibited the acquisition of nicotine-induced place preference. It should be considered that the microinjection of the same doses of WIN 55,212-2 or AM251 into the BLA, by itself had no effect on the CPP score. The administration of a higher dose of AM251 (60 ng/rat) during the acquisition decreased the locomotor activity of animals on the testing phase. Interestingly, the microinjection of AM251 (20 and 40 ng/rat), but not WIN55,212-2 (0.1-0.5 μg/rat), into the BLA inhibited the expression of nicotine-induced place preference without any effect on the locomotor activity. Taken together, these findings support the possible role of endogenous cannabinoid system of the BLA in the acquisition and the expression of nicotine-induced place preference. Furthermore, it seems that there is a functional interaction between the BLA cannabinoid receptors and nicotine in producing the rewarding effects.
在本研究中，检测了向大鼠基底外侧杏仁核（双侧杏仁核内）微量注射大麻素CB1受体激动剂和拮抗剂对尼古丁诱导的位置偏爱效应。采用条件性位置偏爱（CPP）装置评估成年雄性Wistar大鼠中药物的奖赏效应。皮下注射尼古丁（0.2mg/kg）可诱导显著的CPP，且在测试阶段对运动活性无任何影响。向双侧杏仁核内微量注射非选择性大麻素CB1/CB2受体激动剂WIN 55,212-2（0.1-0.5μg/只大鼠）以及无效剂量的尼古丁（0.1mg/kg，皮下注射）可诱导显著的位置偏爱。另一方面，向双侧杏仁核内注射选择性大麻素CB1受体拮抗剂AM251（20-60ng/只大鼠）可抑制尼古丁诱导的位置偏爱的获得。应当注意的是，向双侧杏仁核内注射相同剂量的WIN 55,212-2或AM251本身对CPP评分无影响。在获得阶段给予更高剂量的AM251（60ng/只大鼠）可降低测试阶段动物的运动活性。有趣的是，向双侧杏仁核内注射AM251（20和40ng/只大鼠）而非WIN55,212-2（0.1-0.5μg/只大鼠）可抑制尼古丁诱导的位置偏爱的表达，且对运动活性无任何影响。综上所述，这些发现支持了双侧杏仁核内源性大麻素系统在尼古丁诱导的位置偏爱获得和表达中的可能作用。此外，在产生奖赏效应方面，双侧杏仁核大麻素受体与尼古丁之间似乎存在功能相互作用。
