Key Laboratory of Tropical Biological Resources of Ministry of Education, Key Laboratory for Marine Drugs of Haikou, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
Medical School, Guangxi University, Nanning 530004, China.
Mar Drugs. 2020 Dec 16;18(12):646. doi: 10.3390/md18120646.
Tobacco smoking has become a prominent health problem faced around the world. The α3β4 nicotinic acetylcholine receptor (nAChR) is strongly associated with nicotine reward and withdrawal symptom. α-Conotoxin TxID, cloned from Conus textile, is a strong α3β4 nAChR antagonist, which has weak inhibition activity of α6/α3β4 nAChR. Meanwhile, its analogue [S9K]TxID only inhibits α3β4 nAChR (IC = 6.9 nM), and has no inhibitory activity to other nAChRs. The present experiment investigates the effect of α3β4 nAChR antagonists (TxID and [S9K]TxID) on the expression and reinstatement of nicotine-induced conditioned place preference (CPP) and explores the behaviors of acute nicotine in mice. The animal experimental results showed that TxID and [S9K] TxID could inhibit the expression and reinstatement of CPP, respectively. Moreover, both had no effect in acute nicotine experiment and the locomotor activity in mice. Therefore, these findings reveal that the α3β4 nAChR may be a potential target for anti-nicotine addiction treatment. [S9K]TxID, α3β4 nAChR antagonist, exhibit a superior effect for anti-nicotine addiction, which is promising to develop a novel smoking cessation drug.
吸烟已成为全球面临的一个突出健康问题。α3β4 烟碱型乙酰胆碱受体（nAChR）与尼古丁奖赏和戒断症状密切相关。α-芋螺毒素 TxID 从织纹芋螺中克隆得到，是一种强的α3β4 nAChR 拮抗剂，对α6/α3β4 nAChR 具有较弱的抑制活性。同时，其类似物 [S9K]TxID 仅抑制α3β4 nAChR（IC = 6.9 nM），对其他 nAChR 无抑制活性。本实验研究了α3β4 nAChR 拮抗剂（TxID 和 [S9K]TxID）对尼古丁诱导的条件性位置偏爱（CPP）表达和复燃的影响，并探讨了急性尼古丁对小鼠的行为影响。动物实验结果表明，TxID 和 [S9K]TxID 分别能抑制 CPP 的表达和复燃。此外，两者在急性尼古丁实验中对小鼠的运动活性均无影响。因此，这些发现表明α3β4 nAChR 可能是抗尼古丁成瘾治疗的潜在靶点。α3β4 nAChR 拮抗剂 [S9K]TxID 对尼古丁成瘾具有更好的抑制作用，有望开发新型戒烟药物。
