Unlike lithium, anticonvulsants and antidepressants do not alter rat brain myo-inositol.
Lithium is the first-line in bipolar disorder treatment. Lithium's clinical efficacy might be due to its inhibition of myo-inositol turnover in the phosphatidylinositol second messenger system. This study aimed to determine whether this action can extend to antidepressants and anticonvulsants also used to treat bipolar symptoms. Male rats were treated for 2 weeks with an intraperitoneal injection of phenelzine, fluoxetine, desipramine, carbamazepine, lamotrigine, sodium valproate or vehicle. Brains were dissected and myo-inositol concentrations were analyzed using high-field nuclear magnetic resonance spectroscopy at 18.8 T and quantified using Chenomx Profiler software. Brain regions assessed included the prefrontal, temporal and occipital cortical areas as well as the hippocampus. The main finding is that contrary to lithium, the anticonvulsants and antidepressants do not alter brain myo-inositol concentration. This suggests that these agents might work via a mechanism that is not centered on changes in myo-inositol concentration.
McGrath
Brent M
BM
Department of Psychiatry, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. brent.mcgrath@dal.ca
Greenshaw
Andrew J
AJ
McKay
Ryan
R
Slupsky
Carolyn M
CM
Silverstone
Peter H
PH
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007294:Inositol / Q000378:metabolism*; D000077213:Lamotrigine; D016651:Lithium Carbonate / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D000928:Antidepressive Agents; D018692:Antimanic Agents; D014227:Triazines; D016651:Lithium Carbonate; D002220:Carbamazepine; D007294:Inositol; D014635:Valproic Acid; D000077213:Lamotrigine