Lithium and inositol: effects on brain water homeostasis in the rat.
BACKGROUND
Since its earliest use in psychiatry, lithium has been known to alter body water homeostasis. Although lithium is also known to decrease the concentration of inositol, an important brain osmolyte, little is known of the effects of lithium on brain water homeostasis.


OBJECTIVE
To determine whether lithium alters brain water homeostasis, and, if so, whether the mechanism involves changes in inositol concentration.


METHODS
Rats were fed regular food or regular food plus lithium chloride for either 11 days or 5 weeks. Brains were dissected and assayed for tissue water by the wet-dry method and for inositol by gas chromatography-mass spectrometry.


RESULTS
We found a statistically significant (p=0.05, corrected) 3.1% mean elevation in frontal cortex tissue water in 5-week lithium-fed rats (86.7+/-3.9%), compared to control rats (83.6+/-2.6%). Inositol concentration correlated inversely with percent tissue water (r=-0.50, p=0.003, corrected) in pooled samples of 5-week lithium-fed rats, and was significantly lower in frontal cortex and hippocampus of 5-week lithium-fed rats, compared to controls. Rats fed lithium for 11 days did not differ significantly from controls on either variable.


CONCLUSIONS
This is the first report of a lithium-induced increase in brain tissue water. Although the mechanism is unclear, it does not appear to result from changes in brain inositol concentration or blood sodium concentration. This finding may have implications for the therapeutic or toxic effects of lithium on brain, because increased tissue water can augment cell excitability.
Division of Geriatric Psychiatry, Department of Psychiatry, University of Maryland School of Medicine and the Research Service, VA Maryland Healthcare System, Baltimore, MD 21201, USA.
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P
Phatak
A
A
Shaldivin
L S
LS
King
P
P
Shapiro
W T
WT
Regenold
D000818:Animals; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects; D005625:Frontal Lobe / Q000737:chemistry* / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D007294:Inositol / Q000032:analysis; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000032:analysis*
D014867:Water; D007294:Inositol; D008094:Lithium