Bashiri Hamideh, Rezayof Ameneh, Sahebgharani Mousa, Tavangar Seyed Mohammad, Zarrindast Mohammad-Reza
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 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.
Neuropharmacology. 2016 Jun;105:478-486. doi: 10.1016/j.neuropharm.2016.02.010. Epub 2016 Feb 13.
The present study was designed to clarify whether α2-adrenoceptors of the basolateral amygdala (BLA) are involved in nicotine-induced anxiogenic-like behaviours. Adult male Wistar rats were bilaterally cannulated in the BLA and anxiety-like behaviours were assessed in an elevated plus maze (EPM) task. Systemic intraperitoneal (i.p.) administration of nicotine (0.3, 0.5 and 0.7 mg/kg) dose-dependently decreased open arm time (%OAT) and open arm entry (%OAE), indicating the anxiogenic-like effect of nicotine. The activation of the BLA α2-adrenoceptors by the injection of α2-receptor agonist, clonidine (0.1, 0.3 and 0.5 μg/rat) into the BLA (intra-BLA) reversed nicotine-induced anxiogenic-like behaviours. It is important to note that intra-BLA injection of a higher dose of clonidine (0.5 μg/rat) by itself increased %OAT, but not %OAE which showed an anxiolytic effect of the agonist. On the other hand, intra-BLA injection of different doses of α2-adrenoceptor antagonist, yohimbine (1, 3 and 5 μg/rat) in combination with an ineffective dose of nicotine (0.3 mg/kg) decreased %OAT and %OAE, suggesting a potentiative effect of the antagonist on nicotine response. In addition, intra-BLA injection of the same doses of yohimbine did not alter %OAT and %OAE. Interestingly, intra-BLA injection of yohimbine (0.5 and 1 μg/rat) significantly reversed the inhibitory effect of clonidine on nicotine-induced anxiogenic-like behaviours. It should be considered that the drug treatments had no effect on locomotor activity in all experiments. Taken together, it can be concluded that nicotine produces anxiogenic-like behaviours which may be mediated through the BLA α2-adrenoceptor mechanism.
本研究旨在阐明基底外侧杏仁核(BLA)的α2-肾上腺素能受体是否参与尼古丁诱导的焦虑样行为。成年雄性Wistar大鼠双侧脑内插管至BLA,并在高架十字迷宫(EPM)任务中评估焦虑样行为。腹腔内(i.p.)全身给予尼古丁(0.3、0.5和0.7mg/kg)剂量依赖性地减少了开臂时间(%OAT)和开臂进入次数(%OAE),表明尼古丁具有焦虑样效应。向BLA内注射α2-受体激动剂可乐定(0.1、0.3和0.5μg/只大鼠)(BLA内注射)激活BLA的α2-肾上腺素能受体可逆转尼古丁诱导的焦虑样行为。需要注意的是,BLA内注射较高剂量的可乐定(0.5μg/只大鼠)本身会增加%OAT,但不会增加%OAE,这表明该激动剂具有抗焦虑作用。另一方面,BLA内注射不同剂量的α2-肾上腺素能受体拮抗剂育亨宾(1、3和5μg/只大鼠)与无效剂量的尼古丁(0.3mg/kg)联合使用会降低%OAT和%OAE,表明拮抗剂对尼古丁反应具有增强作用。此外,BLA内注射相同剂量的育亨宾不会改变%OAT和%OAE。有趣的是,BLA内注射育亨宾(0.5和1μg/只大鼠)可显著逆转可乐定对尼古丁诱导的焦虑样行为的抑制作用。应该考虑到,在所有实验中药物治疗对运动活动均无影响。综上所述,可以得出结论,尼古丁产生焦虑样行为,这可能是通过BLA的α2-肾上腺素能受体机制介导的。