Imanishi T, Sawa A, Ichimaru Y, Miyashiro M, Kato S, Yamamoto T, Ueki S
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, Yokohama, Japan.
Eur J Pharmacol. 1997 Mar 5;321(3):273-8. doi: 10.1016/s0014-2999(96)00969-7.
The effects of rolipram, a cAMP-specific phosphodiesterase (phosphodiesterase 4) inhibitor, on experimentally-induced amnesia were examined using a 3-panel runway paradigm in rats and a passive avoidance task in mice. Scopolamine, cerebral ischemia induced by four-vessel occlusion and electric convulsive shock impaired working memory in the 3-panel runway task. Rolipram at 0.1 mg/kg reduced the increase in errors induced by scopolamine or cerebral ischemia. Rolipram at 0.32 mg/kg also reduced the increase in errors induced by electric convulsive shock. Dibutyryl cAMP also had similar effects in 3-panel runway experiments. In the passive avoidance task, rolipram reversed the impairments of the avoidance response induced by scopolamine, cycloheximide and electric convulsive shock at 10, 10 and 3 mg/kg, respectively. These results indicate that rolipram ameliorates impairments of learning and memory in rats and mice, and suggest that rolipram might ameliorate the impairments of learning and memory by elevating cAMP levels.
使用大鼠的三面板跑道范式和小鼠的被动回避任务,研究了环磷腺苷特异性磷酸二酯酶(磷酸二酯酶4)抑制剂咯利普兰对实验性诱导失忆的影响。东莨菪碱、四动脉闭塞诱导的脑缺血和电惊厥休克损害了三面板跑道任务中的工作记忆。0.1mg/kg的咯利普兰减少了由东莨菪碱或脑缺血诱导的错误增加。0.32mg/kg的咯利普兰也减少了由电惊厥休克诱导的错误增加。二丁酰环磷腺苷在三面板跑道实验中也有类似作用。在被动回避任务中,咯利普兰分别在10、10和3mg/kg时逆转了由东莨菪碱、环己酰亚胺和电惊厥休克诱导的回避反应损伤。这些结果表明咯利普兰改善了大鼠和小鼠的学习和记忆损伤,并提示咯利普兰可能通过提高环磷腺苷水平来改善学习和记忆损伤。