Although lithium is the first line of treatment for bipolar disorder, the biological effectiveness of this drug remains unclear. Tetsuo Ohnishi and colleagues from the RIKEN Brain Science Institute and RIKEN BioResource Center have now produced a genetic mouse model to show that lithium’s therapeutic effect stems from its suppression of a biomolecule called myo-inositol.“We set out to examine whether or not the inositol depletion hypothesis of lithium action is real by creating a mouse model in which cellular myo-inositol is reduced genetically,” explains Ohnishi. “If the hypothesis is correct, the mouse model should mimic lithium’s biological effects.” “Lithium exerts antimanic and antidepressive effects in humans, and prolongs the circadian period,” says Ohnishi. “We found an antidepressive trait in our mouse model in various tests, and the circadian period of the model mice was longer than in wild-type controls. Collectively, the data suggest that cellular inositol depletion exerts lithium’s effects.”
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