Intra-Dorsal Hippocampal Microinjections of Lithium and Scopolamine Induce a Cross State-Dependent Learning in Mice

Background: Lithium, a mood stabilizer, may exert adverse effects on memory. We have previously shown that lithium induces state-dependent learning. Cholinergic systems of the brain may play an important role in memory function and mood regulation. In the present study, the effects of intra-dorsal hippocampal (intra-CA1) injections of lithium and scopolamine on memory and cross state-dependent learning between the two drugs were investigated. Methods: For memory assessment, a one-trial step-down inhibitory avoidance task was used in adult male NMRI mice. Results: Intra-CA1 administration of lithium (0.5 and 1 μg/mouse) after training or injection of the drug (0.5μg/mouse) before testing impaired memory when retrieval was tested 24 hours later. The memory impairment by post-training lithium was reversed by pretest administration of the drug (0.5μg/mouse, intra-CA1) suggesting lithium state-dependent learning. On the other hand, intra-CA1 administration of scopolamine (0.5, 1, and 2 μg/mouse) after training or injection of the drug (2μg/mouse) before testing impaired memory when retrieval was tested 24 hours later. The impairment of memory by post-training injection of scopolamine (2μg/mouse) was restored by the pretest injection of the drug (1 and 2 μg/mouse). Furthermore, memory impairment induced by post-training injection of lithium (0.5 μg/mouse) and scopolamine (2 μg/mouse) was reversed by pretest administration of scopolamine (0.5, 1, and 2 μg/mouse) and lithium (0.5 and 1 μg/mouse), respectively. The impairment by lithium was also reversed by physostigmine. Conclusion: The results suggest that microinjections of both lithium and scopolamine induce state-dependent memory and there may be a cross state-dependency between the two drugs.