Effects of Chronic and Acute Lithium Treatment on the Long-term Potentiation and Spatial Memory in Adult Rats.

Objective: Although, accumulating evidence is delineating a neuroprotective and neurotrophic role for lithium (Li), inconsistent findings have also been reported in human studies especially. Moreover, the effects of Li infusion into the hippocampus are still unknown. The aims of this work were (a) to assess whether basal synaptic activity and long-term potentiation (LTP) in the hippocampus are different in regard to intrahippocampal Li infusion; (b) to assess spatial learning and memory in rats chronically treated with LiCO in the Morris water maze.

Methods: Field potentials were recorded form the dentate gyrus, stimulating perforant pathways, in rats chronically (20 mg/kg for 40 days) or acutely treated with LiCO and their corresponding control rats. In addition, performance of rats in a Morris water maze was measured to link behaviour of rats to electrophysiological findings.

Results: LiCO infusion into the hippocampus resulted in enhanced LTP, especially in the late phases, but attenuated LTP was observed in rats chronically treated with Li as compared to controls. Li-treated rats equally performed a spatial learning task, but did spend less time in target quadrant than saline-treated rats in Morris water maze.

Conclusion: Despite most data suggest that Li always yields neuroprotective effects against neuropathological conditions; we concluded that a 40-day treatment of Li disrupts hippocampal synaptic plasticity underlying memory processes, and that these effects of prolonged treatment are not associated with its direct chemical effect, but are likely to be associated with the molecular actions of Li at genetic levels, because its short-term effect preserves synaptic plasticity.