Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids.
OBJECTIVE
There is evidence linking affective disorders and their treatment to alterations in membrane phospholipid metabolism, the phosphatidylinositol (PtdIns) second messenger cycle and brain excitatory and inhibitory amino acids. This study examines lithium effects on rat brain metabolites associated with the above systems and their reversal by myo-inositol.


METHODS
Thirty rats were treated for 14 days with i.p. lithium, saline or lithium plus myo-inositol. 1H, 31P and 7Li NMR were used to measure brain metabolites.


RESULTS
Lithium, administered alone or with myo-inositol, resulted in brain lithium concentrations of approximately 0.6 microM/gram brain tissue. Brain myo-inositol was unchanged when lithium was co-administered with myo-inositol. Lithium increased brain inositol-1-phosphate (I1P) by 98% compared with saline and this effect was not attenuated by the addition of myo-inositol. Lithium treatment decreased phosphatidylserine (PtdSer) and PtdIns by 3% and 8%, respectively. Lithium also decreased taurine levels by 8% and increased aspartate levels by 9%. The above effects of lithium on PtdSer, PtdIns and taurine were attenuated or abolished by the co-administration of myo-inositol.


CONCLUSIONS
Lithium alters levels of key membrane phospholipids and appears to affect the balance between inhibitory and excitatory amino acids in rat brain. Co-administration of myo-inositol attenuates some of these lithium effects on brain metabolites.
Pettegrew
J W
JW
Neurophysics Laboratory, Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. pettegre@pitt.edu
Panchalingam
K
K
McClure
R J
RJ
Gershon
S
S
Muenz
L R
LR
Levine
J
J
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D008094:Lithium / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013654:Taurine / Q000378:metabolism
D000596:Amino Acids; D010716:Phosphatidylinositols; D013654:Taurine; D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase