Tan Rüyal, Bölükbaşi Hatip Funda, Açikalin Öznur, Yamauchi Atsushi, Kataoka Yasufumi, Hatip-Al-Khatib Izzettin
Department of Medical Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Behav Pharmacol. 2018 Jun;29(4):327-335. doi: 10.1097/FBP.0000000000000355.
Nicotinic acetylcholine receptors (nAChRs) are implicated in the pathogenesis of Parkinson's disease (PD). Varenicline tartrate is a partial agonist at α4β2 and full agonist at α7 neuronal nAChR subunits. A unilateral lesion of the substantia nigra (SN) has been used as a reliable model of PD. This study aimed to investigate the effect of varenicline on locomotor and nonlocomotor behavioral deficits induced by a unilateral lesion of the SN induced by 6-hydroxydopamine (6-OHDA) (8 µg/4 µl). Varenicline (1 mg/kg) was administered to the lesioned rats daily for 2 weeks, which commenced 3 weeks after 6-OHDA administration. The results showed that varenicline improved motor deficits induced by 6-OHDA. It improved locomotor and nonlocomotor activities such as forelimb use, rotarod performance, and forelimb asymmetry. Varenicline did not change rearing or vibrissae-elicited forelimb placing but did increase apomorphine-induced rotation. In conclusion, the present results suggest that drugs with specific partial/full agonistic activity on nAChR subunits could be of value in the treatment of neurodegenerative disorders such as PD.
烟碱型乙酰胆碱受体（nAChRs）与帕金森病（PD）的发病机制有关。酒石酸伐尼克兰是α4β2的部分激动剂，也是α7神经元nAChR亚基的完全激动剂。黑质（SN）单侧损伤已被用作PD的可靠模型。本研究旨在探讨伐尼克兰对6-羟基多巴胺（6-OHDA）（8μg/4μl）诱导的SN单侧损伤所致运动和非运动行为缺陷的影响。将伐尼克兰（1mg/kg）每日给予损伤大鼠，持续2周，于6-OHDA给药3周后开始。结果表明，伐尼克兰改善了6-OHDA诱导的运动缺陷。它改善了运动和非运动活动，如前肢使用、转棒试验表现和前肢不对称性。伐尼克兰没有改变竖毛或触须诱发的前肢放置，但确实增加了阿扑吗啡诱导的旋转。总之，目前的结果表明，对nAChR亚基具有特定部分/完全激动活性的药物可能对治疗PD等神经退行性疾病有价值。
