Chronic treatment with lithium increases the ecto-nucleotidase activities in rat hippocampal synatosomes

Lithium is a mood-stabilizing treatment used in bipolar and other psychiatric disorders. The molecular mechanisms underlying lithium action remain poorly understood. Adenosine is a neuromodulator that possesses anticonvulsant and neuroprotective properties and the ecto-nucleotidase pathway is a metabolic source of the extracellular adenosine. Here we investigated the effect of lithium on the ecto-nucleotidase pathway in synaptosomes from hippocampus and cerebral cortex of adult rats. Male Wistar rats received standard rat chow with lithium chloride (2.5 mg/g of chow) and NaCl (17 mg/g of chow) during 4 weeks. The serum lithium levels were 1.18 +/- 0.05 mEq./L. ATP and AMP hydrolysis was significantly increased (20 and 35%, respectively) in hippocampal synaptosomes of rats chronically treated with lithium chloride. No significant differences were observed in the hydrolysis of the three nucleotides by cortical synaptosomes. In conclusion, the modulation of the ecto-nucleotidase pathway may be a new explanation for the potential neuroprotective lithium action in hippocampal lesions.