Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio.
Eur J Neurosci. 2018 Sep;48(5):2110-2117. doi: 10.1111/ejn.14100. Epub 2018 Aug 29.
This study assessed the role of regulator of G protein signaling 2 (RGS2) in nicotine-induced anxiolytic- and antidepressant-like effects using RGS2 wildtype (WT) and RGS2 knockout (KO) mice. RGS2 negatively regulates monoaminergic neurotransmission, which is implicated in the pathology of anxiety and depression. We hypothesized that deletion of RGS2 would enhance nicotine-induced anxiolytic- and antidepressant-like effects, which were assessed using the elevated plus maze and tail suspension tests, respectively. Anxiolytic-like effects were observed in both RGS2 WT and KO mice after administration of low dose of nicotine (0.05 mg/kg, base) compared to respective saline controls. Additionally, administration of nicotine (0.1 mg/kg, base) compared to saline resulted in anxiolytic-like effects in RGS2 KO mice, but not RGS2 WT mice, suggesting genetic deletion of RGS2 facilitated anxiolytic-like effects of nicotine. Administration of nicotine (0.5 and 1 mg/kg, base) compared to saline resulted in antidepressant-like effects in RGS2 WT mice. Antidepressant-like effects were observed in RGS2 KO mice only at the highest tested dose of nicotine (1 mg/kg, base) compared to saline controls, suggesting that genetic deletion of RGS2 decreased sensitivity to antidepressant-like effects of nicotine. Together, the data suggest that RGS2 differentially regulated nicotine-induced affective behavioral responses. These data suggest that individuals with RGS2 polymorphisms may experience differential affective responses to tobacco smoking, which may make them vulnerable to developing nicotine addiction.
这项研究评估了 G 蛋白信号调节因子 2（RGS2）在尼古丁诱导的抗焦虑和抗抑郁样效应中的作用，使用了 RGS2 野生型（WT）和 RGS2 敲除（KO）小鼠。RGS2 负调节单胺能神经传递，这与焦虑和抑郁的病理学有关。我们假设 RGS2 的缺失会增强尼古丁诱导的抗焦虑和抗抑郁样效应，分别使用高架十字迷宫和悬尾试验进行评估。与各自的盐水对照相比，低剂量尼古丁（0.05mg/kg，碱）给药后，RGS2 WT 和 KO 小鼠均表现出抗焦虑样效应。此外，与盐水相比，尼古丁（0.1mg/kg，碱）给药导致 RGS2 KO 小鼠出现抗焦虑样效应，但 RGS2 WT 小鼠没有，表明 RGS2 的遗传缺失促进了尼古丁的抗焦虑样效应。与盐水相比，尼古丁（0.5 和 1mg/kg，碱）给药导致 RGS2 WT 小鼠出现抗抑郁样效应。与盐水对照相比，仅在最高测试剂量的尼古丁（1mg/kg，碱）下，RGS2 KO 小鼠才出现抗抑郁样效应，表明 RGS2 的遗传缺失降低了对尼古丁抗抑郁样效应的敏感性。总之，数据表明 RGS2 差异调节了尼古丁诱导的情感行为反应。这些数据表明，具有 RGS2 多态性的个体可能对烟草吸烟产生不同的情感反应，这可能使他们容易患上尼古丁成瘾。
