Althobaiti Yusuf S
Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
College of Pharmacy, Addiction and Neuroscience Research Unit, Taif University, Taif 21944, Saudi Arabia.
Pharmaceuticals (Basel). 2021 Feb 14;14(2):156. doi: 10.3390/ph14020156.
Quetiapine, an atypical antipsychotic, is effective in the management of schizophrenia, depression, and anxiety. Although quetiapine overdosage and misuse have been reported, its abuse potential has not been investigated in animals. In this study, the abuse potential of quetiapine was assessed based on the conditioned place preference (CPP) paradigm of drug addiction in a mouse model. First, mice received intraperitoneal injections of quetiapine (40, 80, or 120 mg/kg) every other day during the conditioning phase. In the second experiment, mice were pretreated with 0.03 mg/kg SKF-35866, a D1 receptor antagonist, before receiving saline or quetiapine (120 mg/kg) during the conditioning phase. No significant changes in time spent in the quetiapine-paired chamber were observed compared with time spent in the saline-paired chamber in mice treated with 40 or 80 mg/kg. In contrast, the preference to the quetiapine-paired chamber was significantly increased in mice treated with 120 mg/kg quetiapine, and this effect was blocked by SKF-35866 pretreatment. These results demonstrated, for the first time, the abuse potential of quetiapine in an animal model of drug addiction. Interestingly, this CPP-inducing effect was likely mediated by activating D1 receptors.
喹硫平是一种非典型抗精神病药物，对精神分裂症、抑郁症和焦虑症的治疗有效。尽管已有喹硫平过量和滥用的报道，但尚未在动物中研究其滥用潜力。在本研究中，基于药物成瘾的条件性位置偏爱（CPP）范式，在小鼠模型中评估了喹硫平的滥用潜力。首先，在条件化阶段，小鼠每隔一天接受腹腔注射喹硫平（40、80或120mg/kg）。在第二个实验中，在条件化阶段，小鼠在接受生理盐水或喹硫平（120mg/kg）之前，先用0.03mg/kg的D1受体拮抗剂SKF-35866进行预处理。与接受40或80mg/kg喹硫平治疗的小鼠在生理盐水配对室中停留的时间相比，在喹硫平配对室中停留的时间没有观察到显著变化。相反，接受120mg/kg喹硫平治疗的小鼠对喹硫平配对室的偏爱显著增加，并且这种效应被SKF-35866预处理所阻断。这些结果首次证明了喹硫平在药物成瘾动物模型中的滥用潜力。有趣的是，这种诱导CPP的效应可能是通过激活D1受体介导的。
