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Lithium and inositol: effects on brain water homeostasis in the rat

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Abstract

Rationale

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.

Materials and 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.

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Acknowledgements

This research was made possible by funds from the Stanley Medical Research Institute. We are grateful to Ms. Lisa McFarland for her expert help with the GC-MS, and to Dr. Mario Borgnia for his inspiration.

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Authors and Affiliations

  1. 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

    P. Phatak & W. T. Regenold

  2. Stanley Center for Bipolar Research, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheba, Israel

    A. Shaldivin

  3. Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    L. S. King

  4. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, 21201, USA

    P. Shapiro

  5. Department of Psychiatry, University of Maryland Medical Center, Box #351 Room S12A09, 22 South Greene Street, Baltimore, MD, 21201, USA

    W. T. Regenold

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  1. P. Phatak
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  2. A. Shaldivin
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  3. L. S. King
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  4. P. Shapiro
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  5. W. T. Regenold
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Corresponding author

Correspondence to W. T. Regenold.

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This research was made possible by funds from the Stanley Medical Research Institute.

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Phatak, P., Shaldivin, A., King, L.S. et al. Lithium and inositol: effects on brain water homeostasis in the rat. Psychopharmacology 186, 41–47 (2006). https://doi.org/10.1007/s00213-006-0354-y

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  • DOI: https://doi.org/10.1007/s00213-006-0354-y

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