Zupan G, Vitezić D, Mrsić J, Matesić D, Simonić A
Department of Pharmacology, School of Medicine, University of Rijeka, Croatia.
Eur J Pharmacol. 1996 Aug 29;310(2-3):103-6. doi: 10.1016/0014-2999(96)00534-1.
The effects of various doses (0.03, 0.1, 0.3 or 1.0 mg/kg) of the Ca2+ channel blockers nimodipine, felodipine and amlodipine on the learning ability of rats exposed to electroconvulsive shock were examined. The animals were trained in a passive avoidance procedure. The drugs tested were injected 30 min before the learning trial started. The electroconvulsive shock was given immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 h later. It was found that electroconvulsive shock strongly impaired the retention of the passive avoidance response. Nimodipine, felodipine and amlodipine did not influence the passive avoidance behavior in the sham electroconvulsive shock group, but significantly improved the retention deficits in the animals exposed to electroconvulsive shock. These findings support the hypothesis that perturbations in Ca2+ homeostasis can contribute to the memory deficits associated with electroconvulsive shock. The antiamnestic effects of the substances tested make them interesting candidates for clinical trials in patients with cognitive impairment caused by electroconvulsive shock therapy.
研究了不同剂量(0.03、0.1、0.3或1.0毫克/千克)的钙通道阻滞剂尼莫地平、非洛地平和氨氯地平对遭受电休克的大鼠学习能力的影响。动物在被动回避程序中接受训练。在学习试验开始前30分钟注射受试药物。在获得学习试验反应后立即给予电休克。24小时后进行被动回避保持试验。发现电休克严重损害了被动回避反应的保持。尼莫地平、非洛地平和氨氯地平在假电休克组中不影响被动回避行为,但显著改善了遭受电休克动物的保持缺陷。这些发现支持了以下假设,即钙稳态的紊乱可能导致与电休克相关的记忆缺陷。受试物质的抗遗忘作用使其成为电休克治疗所致认知障碍患者临床试验的有趣候选药物。