Effects of chronic lithium and sodium valproate on concentrations of brain amino acids.
The present study was designed to determine if the mood stabilizers, lithium and valproate, have common effects on concentrations of amino acid neurotransmitters which may be related to their mechanisms of action. Two separate groups of rats were administered therapeutic doses of lithium, sodium valproate, or saline for 2 weeks. Whole brain extracts were then examined using either high-field 1H NMR spectroscopy or HPLC. Both drugs decreased whole brain concentrations of aspartate, glutamate, and taurine while brain concentrations of gamma-aminobutyric acid (GABA) and alanine decreased following chronic sodium valproate administration but not following chronic lithium administration. These findings indicate that lithium and sodium valproate share common effects on the concentrations of certain amino acid neurotransmitters in whole brain which may be related to their mechanisms of action in bipolar disorder.
O'Donnell
T
T
Department of Psychiatry, University of Alberta Hospital, Edmonton, AB T6G 2B7, Canada.
Rotzinger
S
S
Ulrich
M
M
Hanstock
C C
CC
Nakashima
T T
TT
Silverstone
P H
PH
D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D004791:Enzyme Inhibitors; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D008094:Lithium; D000409:Alanine