Abstract
Rationale
Lithium has been a standard pharmacological treatment for bipolar disorder over the last 60 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. Attenuation of the phosphatidylinositol signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as one of the possible mechanisms for lithium-induced mood stabilization.
Objectives
The objective was to study the behavioral effect of the specific competitive IMPase inhibitor L-690,330 in mice in the lithium-sensitive pilocarpine-induced seizures paradigm and the forced swim test (FST).
Methods
The inhibitor was administered intracerebroventricularly in liposomes.
Results
L-690,330 increased the sensitivity to subconvulsive doses of pilocarpine and decreased immobility time in the FST.
Conclusions
It is possible that the behavioral effects of lithium in the pilocarpine-induced seizures and in the FST are mediated through the inhibition of IMPase, but reversal of the inhibitor’s effect with intracerebroventricular inositol would be an important further step in proof.
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Shtein, L., Toker, L., Bersudsky, Y. et al. The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test. Psychopharmacology 227, 503–508 (2013). https://doi.org/10.1007/s00213-013-2969-0
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DOI: https://doi.org/10.1007/s00213-013-2969-0