title: Inositol-deficient food augments a behavioral effect of long-term lithium treatment mediated by inositol monophosphatase inhibition: an animal model with relevance for bipolar disorder.
abstract: Lithium treatment in rodents markedly enhances cholinergic agonists such as pilocarpine. This effect can be reversed in a stereospecific manner by administration of inositol, suggesting that the effect of lithium is caused by inositol monophosphatase inhibition and consequent inositol depletion. If so, inositol-deficient food would be expected to enhance lithium effects. Inositol-deficient food was prepared from inositol-free ingredients. Mice with a homozygote knockout of the inositol monophosphatase 1 gene unable to synthesize inositol endogenously and mimicking lithium-treated animals were fed this diet or a control diet. Lithium-treated wild-type animals were also treated with the inositol-deficient diet or control diet. Pilocarpine was administered after 1 week of treatment, and behavior including seizures was assessed using rating scale. Inositol-deficient food-treated animals, both lithium treated and with inositol monophosphatase 1 knockout, had significantly elevated cholinergic behavior rating and significantly increased or earlier seizures compared with the controls. The effect of inositol-deficient food supports the role of inositol depletion in the effects of lithium on pilocarpine-induced behavior. However, the relevance of this behavior to other more mood-related effects of lithium is not clear.
authors: From the *Department of Clinical Biochemistry and Pharmacology, †Psychiatry Research Unit, and ‡Faculty of Health Sciences, Ben-Gurion University of the Negev; and §Mental Health Center, Beersheva, Israel.
authors: Liza
authors: L
authors: Shtein
authors: Galila
authors: G
authors: Agam
authors: R H
authors: RH
authors: Belmaker
authors: Yuly
authors: Y
authors: Bersudsky
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000627:therapeutic use*; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007294:Inositol / Q000172:deficiency*; D018020:Lithium Compounds / Q000627:therapeutic use*; D051379:Mice; D008813:Mice, Inbred ICR; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010862:Pilocarpine; D014804:Vitamin B Deficiency / Q000523:psychology*
chemical_list: D018692:Antimanic Agents; D004791:Enzyme Inhibitors; D018020:Lithium Compounds; D010862:Pilocarpine; D007294:Inositol; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase