Ekici Abdurrahman, Gürbüz Esra, Berköz Mehmet, Türkmen Ömer, Başbuğan Yıldıray, Yunusoğlu Oruç
Department of Parasitology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.
Gen Physiol Biophys. 2022 May;41(3):245-253. doi: 10.4149/gpb_2022014.
Alcohol addiction or alcoholism constitutes a significant risk factor worldwide for morbidity and mortality. Moxidectin is a recently approved anthelmintic drug, which also activates the gamma-aminobutyric acid receptors. The objective of the present study was to examine the impact of moxidectin on rewarding effects of ethanol in the conditioned place preference (CPP) model in mice. In separate experiments, mice were administered intraperitoneal (i.p.) injections of moxidectin (5 or 10 mg/kg, i.p.) before a) acquisition of alcohol-induced CPP, b) each extinction session, and c) alcohol-induced reinstatement of CPP. The present experiments provide consistent data about ethanol place preference in mice (2 g/kg, i.p.), with mice in all tests spending significantly more time on the ethanol-paired side. The acquisition of the CPP response to ethanol was prevented by the administration of moxidectin at a dose of 10 mg/kg. Additionally, moxidectin treatment accelerated the extinction of ethanol CPP when given repeatedly during the extinction phase. Ethanol-induced reinstatement of CPP following an extinction phase was inhibited by moxidectin. Ethanol alone and co-administration with moxidectin did not change locomotor activity and motor coordination. In conclusion, we suggest that moxidectin may be a promising therapeutic candidate for prevention of ethanol-induced addiction and relapse as well as detoxification.
酒精成瘾或酒精中毒是全球范围内导致发病和死亡的一个重要风险因素。莫昔克丁是一种最近获批的驱虫药,它还能激活γ-氨基丁酸受体。本研究的目的是在小鼠条件性位置偏爱(CPP)模型中检测莫昔克丁对乙醇奖赏效应的影响。在单独的实验中,在以下情况之前给小鼠腹腔注射莫昔克丁(5或10毫克/千克,腹腔注射):a)获得酒精诱导的CPP时,b)每次消退试验时,以及c)酒精诱导的CPP恢复时。本实验提供了关于小鼠对乙醇位置偏爱的一致数据(2克/千克,腹腔注射),在所有试验中,小鼠在与乙醇配对的一侧花费的时间显著更多。以10毫克/千克的剂量给予莫昔克丁可阻止对乙醇的CPP反应的获得。此外,在消退阶段重复给予莫昔克丁治疗可加速乙醇CPP的消退。莫昔克丁可抑制消退阶段后乙醇诱导的CPP恢复。单独使用乙醇以及乙醇与莫昔克丁联合使用均未改变运动活性和运动协调性。总之,我们认为莫昔克丁可能是预防乙醇诱导的成瘾、复发以及解毒的一种有前景的治疗候选药物。