.The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test Academic Article uri icon

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.

publication date

  • January 1, 2013