Akar Furuzan, Mutlu Oguz, Komsuoglu Celikyurt Ipek, Ulak Guner, Erden Faruk, Bektas Emine, Tanyeri Pelin
Department of Pharmacology, Medical Faculty, Kocaeli University, Kocaeli, Turkey.
Department of Pharmacology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.
Med Sci Monit Basic Res. 2014 Jul 24;20:105-11. doi: 10.12659/MSMBR.891149.
Phosphodiesterase (PDE) inhibitors in the central nervous system have been shown to stimulate neuronal functions and increase neurogenesis in Alzheimer disease (AD) patients.
MATERIAL/METHODS: The aim of this study was to investigate the effects of zaprinast, a PDE5 inhibitor, and rolipram, a PDE4 inhibitor, on learning and memory in elevated plus maze (EPM) and passive avoidance (PA) tests in naive mice. Male Balb-c mice received short-term treatment with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) before the acquisition trial of the EPM and PA tests. The exploratory activity of the animals was also investigated in the Hughes box test.
Both zaprinast (10 mg/kg) and rolipram (0.1 mg/kg) significantly decreased second-day latency compared to the control group in the EPM test, while only rolipram (0.1 mg/kg) significantly increased second-day latency in the PA test. Both zaprinast (10 mg/kg) and rolipram (0.1 mg/kg) significantly decreased the number of entries to new areas and time spent in new areas in the Hughes box test.
Our study revealed that both zaprinast and rolipram enhanced spatial memory in EPM, while rolipram seemed to have more emotional memory-enhancing effects in the PA test compared to zaprinast. Both zaprinast and rolipram diminished exploratory activity in the Hughes box test, which can be attributed to the drugs' anxiogenic effects.
中枢神经系统中的磷酸二酯酶(PDE)抑制剂已被证明可刺激阿尔茨海默病(AD)患者的神经元功能并增加神经发生。
材料/方法:本研究的目的是在高架十字迷宫(EPM)和被动回避(PA)试验中,研究PDE5抑制剂扎普司特和PDE4抑制剂咯利普兰对未接触过药物的小鼠学习和记忆的影响。雄性Balb-c小鼠在EPM和PA试验的习得性试验前接受扎普司特(3和10 mg/kg)和咯利普兰(0.05和0.1 mg/kg)的短期治疗。还在休斯箱试验中研究了动物的探索活动。
在EPM试验中,与对照组相比,扎普司特(10 mg/kg)和咯利普兰(0.1 mg/kg)均显著缩短了第二天的潜伏期,而在PA试验中,只有咯利普兰(0.1 mg/kg)显著延长了第二天的潜伏期。在休斯箱试验中,扎普司特(10 mg/kg)和咯利普兰(0.1 mg/kg)均显著减少了进入新区域的次数和在新区域花费的时间。
我们的研究表明,扎普司特和咯利普兰均可增强EPM中的空间记忆,而与扎普司特相比,咯利普兰在PA试验中似乎具有更强的增强情绪记忆的作用。在休斯箱试验中,扎普司特和咯利普兰均降低了探索活动,这可能归因于药物的致焦虑作用。