University of Health Sciences Bursa Yuksek Ihtisas Training and Research Hospital, 16290, Bursa, Turkey.
Department of Medical Pharmacology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.
Neurosci Lett. 2021 Jun 11;755:135913. doi: 10.1016/j.neulet.2021.135913. Epub 2021 Apr 22.
Schizophrenia modeling by disrupting prepulse inhibition (PPI) is one of the most frequently used psycho-pharmacological methods by administering pharmacological agents to stimulate disruption. However, since PPI is also a biological indicator of schizophrenia, it is possible to classify subjects based on their basal PPI values and group them as "low inhibition" and "high inhibition without taking any pharmacological agent. Therefore this study was conducted to show that rats can be divided into groups in terms of susceptibility to schizophrenia according to basal PPI values. It was also observed that these groups might give different responses to different pharmacological agents (apomorphine, amphetamine, MK-801, scopolamine, nicotine, caffeine). Male Sprague Dawley rats (250-350 g) were used in the study. To examine the effects of different pharmacological agents on the groups, apomorphine (0.5 mg/kg and 1 mg/kg), amphetamine (4 mg/kg), MK-801 (0.05 mg/kg and 0.15 mg/kg), scopolamine (0.4 mg/kg), nicotine (1 mg/kg) and caffeine (10 mg/kg and 30 mg/kg) were used. Amphetamine showed a disruptive effect on PPI in both low and high inhibitory groups, while apomorphine, MK-801, scopolamine, and nicotine showed PPI decrease only in the high inhibitory group. Besides, caffeine decreased PPI levels at two doses in the high inhibitory group; however, 10 mg/kg dose caffeine was increased only in the low inhibitory group. According to the data obtained from this study, rats can be grouped with baseline inhibition values by using PPI, and response differences of pharmacological agents to groups may vary.
通过破坏条件性回避(PPI)来模拟精神分裂症是最常使用的精神药理学方法之一,通过给予药物刺激破坏来实现。然而,由于 PPI 也是精神分裂症的生物学指标,因此可以根据基础 PPI 值对受试者进行分类,并将其分为“低抑制”和“高抑制”,而无需使用任何药物。因此,本研究旨在表明,根据基础 PPI 值,大鼠可以分为对精神分裂症易感性不同的组。还观察到,这些组可能对不同的药物(阿扑吗啡、安非他命、MK-801、东莨菪碱、尼古丁、咖啡因)产生不同的反应。本研究使用雄性 Sprague Dawley 大鼠(250-350g)。为了研究不同药物对各组的影响,使用了阿扑吗啡(0.5mg/kg 和 1mg/kg)、安非他命(4mg/kg)、MK-801(0.05mg/kg 和 0.15mg/kg)、东莨菪碱(0.4mg/kg)、尼古丁(1mg/kg)和咖啡因(10mg/kg 和 30mg/kg)。安非他命对低抑制和高抑制组的 PPI 均有破坏作用,而阿扑吗啡、MK-801、东莨菪碱和尼古丁仅在高抑制组中表现出 PPI 下降。此外,咖啡因在高抑制组的两个剂量下均降低了 PPI 水平;然而,仅在低抑制组中,10mg/kg 剂量的咖啡因增加了 PPI 水平。根据本研究获得的数据,大鼠可以通过 PPI 基于基础抑制值进行分组,并且药物对组的反应差异可能会有所不同。