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. 2013 Jun;227(3):503-8.
doi: 10.1007/s00213-013-2969-0. Epub 2013 Jan 24.

The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test

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The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test

Liza Shtein et al. Psychopharmacology (Berl). 2013 Jun.

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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