Abstract

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 mu mol/l H-89 into the CA1 region of the hippocampus. Animals were then tested 48 h after H-89 infusion inorder 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-89treated animals. The data suggest that lithium treatment for 4 weeks improved spatial memory retention and that lithium pretreatment prevented or reversed the H-89induced spatial memory deficits. Copyright (c) 2007 S. Karger AG, Basel.