Sharifzadeh Mohammad, Aghsami Mehdi, Gholizadeh Shervin, Tabrizian Kaveh, Soodi Maliheh, Khalaj Siavash, Ranjbar Akram, Hosseini-Sharifabad Ali, Roghani Ali, Karimfar Mohammad H
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Pharmacology. 2007;80(2-3):158-65. doi: 10.1159/000103265. Epub 2007 Jan 8.
We have previously shown that infusion of the PKAII inhibitor H-89 in the CA1 area of the hippocampus impaired spatial memory retention. There is some evidence suggesting the neuroprotective effects of chronic lithium administration including its ability to attenuate a deleterious effect of chronic stress on spatial memory in rats. In the present study, we investigated whether chronic administration of lithium can improve memory as well as influence the inhibitory effect of H-89 on spatial memory retention. Male albino rats were treated systemically with lithium (600 mg/l) for 4 weeks and then trained for 4 days in the Morris water maze. Testing the animals 48 h later showed a significant reduction in escape latency (p < 0.05) and travel distance (p < 0.05) compared to the controls. In separate experiments, the rats were similarly treated with lithium for 4 weeks, followed by similar training for 4 days and then immediately infused bilaterally with vehicle or 5 micromol/l H-89 into the CA1 region of the hippocampus. Animals were then tested 48 h after H-89 infusion in order to assess their spatial memory retention. The lithium treatment caused a significant reduction in escape latency (p < 0.001) and travel distance (p < 0.001) compared to H-89-treated animals. The data suggest that lithium treatment for 4 weeks improved spatial memory retention and that lithium pretreatment prevented or reversed the H-89-induced spatial memory deficits.
我们之前已经表明，在海马体CA1区域注入PKAII抑制剂H-89会损害空间记忆的保持。有一些证据表明，长期给予锂盐具有神经保护作用，包括其减轻慢性应激对大鼠空间记忆有害影响的能力。在本研究中，我们调查了长期给予锂盐是否能改善记忆，以及是否会影响H-89对空间记忆保持的抑制作用。雄性白化大鼠全身给予锂盐（600 mg/l）4周，然后在莫里斯水迷宫中训练4天。48小时后对动物进行测试，结果显示与对照组相比，逃避潜伏期（p < 0.05）和游动距离（p < 0.05）显著缩短。在单独的实验中，大鼠同样接受锂盐治疗4周，接着进行4天类似的训练，然后立即双侧海马体CA1区域注入溶剂或5 μmol/l H-89。在注入H-89 48小时后对动物进行测试，以评估其空间记忆保持情况。与接受H-89治疗的动物相比，锂盐治疗使逃避潜伏期（p < 0.001）和游动距离（p < 0.001）显著缩短。数据表明，4周的锂盐治疗改善了空间记忆保持，并且锂盐预处理预防或逆转了H-89诱导的空间记忆缺陷。
