IP3 accumulation and/or inositol depletion: two downstream lithium's effects that may mediate its behavioral and cellular changes.

ABSTRACT: Lithium is the prototype mood stabilizer but its mechanism is still unresolved. Two hypotheses dominate-the consequences of lithium's inhibition of inositol monophosphatase at therapeutically relevant concentrations (the 'inositol depletion' hypothesis), and of glycogen-synthase kinase-3. To further elaborate the inositol depletion hypothesis that did not decisively determine whether inositol depletion per se, or phosphoinositols accumulation induces the beneficial effects, we utilized knockout mice of either of two inositol metabolism-related genes-IMPA1 or SMIT1, both mimic several lithium's behavioral and biochemical effects. We assessed in vivo, under non-agonist-stimulated conditions, ³H-inositol incorporation into brain phosphoinositols and phosphoinositides in wild-type,

SUBMITTER: Sade Y 

PROVIDER: S-EPMC5315558 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature