title: Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo magnetic resonance spectroscopy study at 18.8 T.
abstract: Lithium has been the mainstay of treatment for bipolar disorder. Early studies suggest that lithium acts via inositol depletion. This study assesses the effect of 1, 2 and 4 weeks of lithium treatment on myo-inositol concentrations across several brain regions. Thirty-six Sprague-Dawley rats were treated for 2 weeks with an intraperitoneal injection of either 1 mmol/kg/day, twice daily lithium chloride (n=18) or placebo (2 ml/kg of saline) (n=18). The rats were separated into three groups: 1 week, 2 weeks and 4 weeks. Brains were dissected into prefrontal, temporal and occipital cortical areas, as well as hippocampus, and analyzed at 18.8 T. Myo-inositol was quantified using the Chenomx Profiler software. Lithium did not alter myo-inositol concentrations at 1 week. A significant reduction exists in myo-inositol concentrations in lithium-treated rats at 2 and 4 weeks, across all four brain regions. Studies suggest brain region-specific alterations in myo-inositol concentrations among bipolar patients. Our findings suggest that lithium-induced reduction of myo-inositol is more global.
authors.affiliation: Department of Psychiatry, National High Field Magnetic Resonance Centre, University of Alberta, Edmonton, Alberta, Canada. brent.mcgrath@ualberta.ca
authors.forename: Brent M
authors.initials: BM
authors.lastname: McGrath
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Greenshaw
authors.forename: Ryan
authors.initials: R
authors.lastname: McKay
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Slupsky
authors.forename: Peter H
authors.initials: PH
authors.lastname: Silverstone
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004334:Drug Administration Schedule; D007294:Inositol / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D018692:Antimanic Agents; D007294:Inositol; D018021:Lithium Chloride