Neurochemistry and Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
Neurochemistry and Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan/Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Pak J Pharm Sci. 2021 Jan;34(1):135-141.
Present study was designed to monitor the dose dependent effects of lorazepam; a benzodiazepine (CNS depressant). It is the primary drug of choice for treatment of anxiety and to produce calming effects. However, repeated administration of this lorazepam causes dependence and this might be caused by increased dopaminergic neurotransmission. Besides dopamine, 5-hydroxy tryptamine (5-HT) has also been reported to have pivotal role in the pathophysiology as well as treatment of anxiety and addiction. Repeated administration of lorazepam might involve altered 5-HT metabolism as well. Present study was therefore designed to monitor dose-dependent effects of lorazepam and to select its optimum dose for further experiments and pharmacological interventions. Effects of lorazepam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, forced swim test and metabolism of dopamine and 5-HT. oral administration of lorazepam was done at the doses of 0mg/kg, 2mg/kg, 4mg/kg and 6mg/kg. Behaviors parameters were monitored following single administration of lorazepam. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of lorazepam and related benzodiazepines.
本研究旨在监测劳拉西泮(一种苯二氮䓬类药物,中枢神经系统抑制剂)的剂量依赖性作用。它是治疗焦虑症和产生镇静作用的首选药物之一。然而,劳拉西泮的重复给药会导致依赖性,这可能是由于多巴胺能神经传递增加所致。除了多巴胺,5-羟色胺(5-HT)也被报道在焦虑症和成瘾的病理生理学以及治疗中具有关键作用。劳拉西泮的重复给药也可能涉及 5-HT 代谢的改变。因此,本研究旨在监测劳拉西泮的剂量依赖性作用,并选择其最佳剂量用于进一步的实验和药理学干预。通过 HPLC-EC 对大鼠全脑样本进行神经化学分析,监测劳拉西泮对食物摄入、生长速度、熟悉和新环境中的活动、明暗箱活动、强迫游泳试验以及多巴胺和 5-HT 代谢的影响。劳拉西泮的口服剂量分别为 0mg/kg、2mg/kg、4mg/kg 和 6mg/kg。单次给予劳拉西泮后监测行为参数。大鼠断头后收集全脑样本,储存在-70°C 直至进行 HPLC-EC 分析。本研究的结果可能与劳拉西泮和相关苯二氮䓬类药物的治疗效用增加有关。