Desipramine attenuates forced swim test-induced behavioral and neurochemical alterations in mice: an in vivo(1)H-MRS study at 9.4T.
The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ((1)H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5000/20/2.2ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7microl) and hippocampus (6microl) of C57BL/6 mice at 9.4T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine+phosphocreatine (Cr+PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development.
Kim
Sang-Young
SY
Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Lee
Yun-Jung
YJ
Kim
Hyeonjin
H
Lee
Do-Wan
DW
Woo
Dong-Cheol
DC
Choi
Chi-Bong
CB
Chae
Jeong-Ho
JH
Choe
Bo-Young
BY
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D010725:Phosphocreatine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011522:Protons; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D013550:Swimming / Q000523:psychology
D004791:Enzyme Inhibitors; D011522:Protons; D010725:Phosphocreatine; D005973:Glutamine; D007294:Inositol; D003401:Creatine; D002794:Choline; D003891:Desipramine