Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA; Department of Pharmacology and Toxicology, King Saud University, Riyadh, Saudi Arabia.
Behav Brain Res. 2019 Mar 15;360:262-269. doi: 10.1016/j.bbr.2018.12.027. Epub 2018 Dec 12.
The objective of the present study is to investigate the role of α4, α5, α6 or β2 nAChR subunits in the antidepressant-like effect of bupropion. Adult male mice were treated with subcutaneous acute doses of bupropion (3 and 10 mg/kg) 30 min before the forced swim test (FST) in α4, α5, α6, or β2 nAChR subunit knockout (KO) and wild-type (WT) mice. In addition, the effects of β2* antagonist dihydro-β-erythroidine (DHβE, 3 mg/kg) on antidepressant-like effects of bupropion in C57BL/6 J mice were assessed. Our results showed that baseline immobility and climbing time did not differ between KO and corresponding WT mice except for β2 KO. Bupropion significantly decreased immobility time and increased climbing time in the α4, α6 and β2 nAChR KO mice in comparison to WT littermates, indicating that lack of these nAChR subunits enhanced antidepressant effects of bupropion. On the contrary, the α5 nAChR subunit deletion did not alter the FST behavior in the bupropion-treated mice. Not only in the transgenic mice, bupropion also showed antidepressant-like effects in the WT mice. In addition, DHβE pretreatment before bupropion administration resulted in decreased immobility time and increased climbing time. Taken together, the present study provides evidence on the involvement of α4*, α6*, and β2* (* indicates possible presence of other subunits) nAChRs in the antidepressant-like effects of bupropion in the FST.
本研究旨在探讨 α4、α5、α6 或 β2 烟碱型乙酰胆碱受体亚基在安非他酮抗抑郁样作用中的作用。成年雄性小鼠在强迫游泳试验（FST）前 30 分钟接受皮下急性安非他酮（3 和 10mg/kg）处理，在 α4、α5、α6 或 β2 烟碱型乙酰胆碱受体亚基敲除（KO）和野生型（WT）小鼠中进行。此外，还评估了β2拮抗剂二氢-β-erythroidine（DHβE，3mg/kg）对 C57BL/6 J 小鼠安非他酮抗抑郁样作用的影响。我们的结果表明，除了β2 KO 之外，KO 和相应 WT 小鼠之间的基础不动时间和攀爬时间没有差异。与 WT 同窝仔相比，安非他酮显著降低了 α4、α6 和 β2 nAChR KO 小鼠的不动时间，增加了攀爬时间，表明缺乏这些 nAChR 亚基增强了安非他酮的抗抑郁作用。相反，α5 nAChR 亚基缺失并没有改变安非他酮处理小鼠的 FST 行为。不仅在转基因小鼠中，安非他酮在 WT 小鼠中也表现出抗抑郁样作用。此外，DHβE 预处理后再给予安非他酮可减少不动时间，增加攀爬时间。总之，本研究为 α4、α6* 和 β2*（*表示可能存在其他亚基）nAChRs 在 FST 中参与安非他酮抗抑郁样作用提供了证据。
