Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo magnetic resonance spectroscopy study at 18.8 T.
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.
McGrath
Brent M
BM
Department of Psychiatry, National High Field Magnetic Resonance Centre, University of Alberta, Edmonton, Alberta, Canada. brent.mcgrath@ualberta.ca
Greenshaw
Andrew J
AJ
McKay
Ryan
R
Slupsky
Carolyn M
CM
Silverstone
Peter H
PH
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
D018692:Antimanic Agents; D007294:Inositol; D018021:Lithium Chloride