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Journal of Neural Transmission

, Volume 104, Issue 2–3, pp 299–305 | Cite as

Inositol has behavioral effects with adaptation after chronic administration

  • H. Cohen
  • M. Kotler
  • Z. Kaplan
  • M. A. Matar
  • O. Kofman
  • R. H. Belmaker
Biological Psychiatry

Summary

Inositol is a simple dietary polyol that serves as a precursor in important second messenger systems. Inositol in pharmacological doses has been reported recently to be therapeutic in depression, panic disorder and obsessive compulsive disorder. We hereby report effects of inositol in the elevated plus maze model of anxiety. These results should allow development of new inositol analogs that could expand psychoactive drug development possibilities via second messenger manipulation.

Keywords

Inositol PI cycle anxiety animal model 

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References

  1. Arendrup K, Gregersen G, Hawley J, Hawthorne JN (1989) High-dose dietary myoinositol supplementation does not alter the ischemia phenomenon in human diabetics. Acta Neurol Scand 80: 99–102PubMedGoogle Scholar
  2. Agam G, Shapiro J, Bersudsky Y, Kofman O, Belmaker RH (1994) High-dose peripheral inositol raises brain inositol levels and reverses behavioral effects of inositol depletion by lithium. Pharmacol Biochem Behav 49: 341–343PubMedGoogle Scholar
  3. Baraban JM, Worley PF, Snyder SH (1989) Second messenger systems and psychoactive drug action: focus on the phosphoinositol system and lithium. Am J Psychiatry 146: 1251–1260PubMedGoogle Scholar
  4. Batty HI, Downes CP (1995) The mechanism of muscarinic receptor-stimulated phosphatidylinositol resynthesis in 1321N1 astrocytoma cells and its inhibition by Li+. J Neurochem 65(5): 2279–2289PubMedGoogle Scholar
  5. Belmaker RH, Bersudsky Y, Benjamin J, Agam G, Levine J, Kofman O (1995) Manipulation of inositol-linked second messenger systems as a therapeutic strategy in psychiatry. In: Gessa G, Fratta W, Pani L, Serra G (eds) Depression and mania. From neurobiology to treatment. Raven Press, New YorkGoogle Scholar
  6. Benjamin J, Levine J, Fux M, Aviv A, Levy D, Belmaker RH (1995) Inositol treatment for panic disorder: a double-blind placebo-controlled crossover trial. Am J Psychiatry 152: 1081–1086PubMedGoogle Scholar
  7. Bersudsky Y, Vinnitsky I, Grisaru N, Kofman O, Belmaker RH (1993) Dose-response and time-curve of inositol prevention of Li-pilocarpine seizures. Eur Neuropsychopharmacol 2 [Special issue]: 428–429Google Scholar
  8. Cohen H, Bar-Haim N, Kotler M (1996) Acute inositol induces anxiety in rats. Biol Psychiatry 40: 426–427PubMedGoogle Scholar
  9. Crawley JN (1994) Interactions between cholecystokinin and other neurotransmitter systems. In: Bradwejn J (ed) Cholecystokinin and anxiety. From neuron to behavior. Biomédical Publishers, CRC PressGoogle Scholar
  10. File SE (1993) The interplay of learning and anxiety in the elevated plus maze. Behav Brain Res 58(1–2): 199–202PubMedGoogle Scholar
  11. Fux M, Levine J, Aviv A, Belmaker RH (1966) Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry 153: 1219–1221Google Scholar
  12. Ghalayini A, Eichberg J (1985) Purification of phosphatidylinositol synthetase from rat brain by CDP-diacylglycerol affinity chromatography and properties of the purified enzyme. J Neurochem 44: 175–182PubMedGoogle Scholar
  13. Greene DA, Brown MJ, Braunstein SN, Schwartz SS, Asbury AA, Winegrad AI (1981) Comparison of clinical course and sequential electrophysiological tests in diabetics with symptomatic polyneuropathy and its implications for clinical trials. Diabetes 30: 139–147PubMedGoogle Scholar
  14. Hallman M (1984) Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung. Biochim Biophys Acta 795: 67–78PubMedGoogle Scholar
  15. Hallman M, Jarvenpaa AL, Pohjavuori (1986) Respiratory distress syndrome and inositol supplementation in preterm infants. Arch Dis Childhood 61: 1076–1083Google Scholar
  16. Hallman M, Bry K, Hoppu K, Lapp M, Pohjavuori M (1992) Inositol supplementation in premature infants with respiratory distress syndrome. N Engl J Med 326: 1233–1239PubMedGoogle Scholar
  17. Jope RS, Williams MB (1994) Lithium and brain signal transduction systems. Biochem Pharmacol 47: 429–434PubMedGoogle Scholar
  18. Kim J, Kyriazi H, Greene DA (1991) Normalization of NA+-K+-ATPase activity in isolated membrane fraction from sciatic nerves of streptozocin-induced diabetic rats by dietary myo-inositol supplementation in vivo or protein kinase C agonists in vitro. Diabetes 40: 558–567PubMedGoogle Scholar
  19. Kofman O, Sherman WR, Katz V, Belmaker RH (1993) Restoration of brain myoinositol levels in rats increases latency to lithium-pilocarpine seizures. Psychopharmacology 110: 229–234PubMedGoogle Scholar
  20. Kofman O, Belmaker RH (1993a) Biochemical, behavioral and clinical studies of the role of inositol in lithium treatment and depression. Biol Psychiatry 34: 839–852PubMedGoogle Scholar
  21. Kofman O, Bersudsky Y, Vinnitsky I, Alpert C, Belmaker RH (1993b) The effect of peripheral inositol injection on rat motor activity models of depression. Israel J Med Sci 29: 580–586PubMedGoogle Scholar
  22. Levine J, Goldberger I, Rapaport A, Schwarts M, Schilds C, Elizur A, Belmaker RH, Shapiro J, Agam G (1994) CSF inositol levels in schizophrenia are unchanged and inositol is not therapeutic in anergic schizophrenia. Eur Neuropsychopharmacol 4: 487–490PubMedGoogle Scholar
  23. Levine J, Barak Y, Gonsalves M, Szor H, Elizur A, Kofman O, Belmaker RH (1995a) A double-blind controlled trial of inositol treatment of depression. Am J Psychiatry 152: 792–794PubMedGoogle Scholar
  24. Levine J, Ring A, Barak Y, Elizur A, Belmaker RH (1995b) Inositol may worsen attention deficit disorder with hyperactivity. Hum Psychopharmacol 10: 481–484Google Scholar
  25. Manji HK, Bersudsky B, Chen G, Belmaker RH, Potter WZ (1996) Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol. Neuropsychopharmacology 15: 370–381PubMedGoogle Scholar
  26. Patishi Y, Lubrich B, Berge M, Kofman O, Van Calker D, Belmaker RH (1996) Differential uptake of myo-inositol in vivo into rat brain areas. Eur Neuropsychopharmacol 6: 73–75PubMedGoogle Scholar
  27. Rahman S, Neuman RS (1993) Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization. Brain Res 631: 349–351PubMedGoogle Scholar
  28. Ramos RT, Gentil V, Gorenstein C (1993) Clomipramine and initial worsening in panic disorder: beyond the “jitteriness syndrome”. J Psychopharmacol 7(3): 265–269Google Scholar
  29. Reynolds JEF (1993) Martindale: the extra pharmacopoeia, 30th ed. The Pharmaceutical Press, LondonGoogle Scholar
  30. Rodriguez SA, Martin MT, Fernandez E, Gonalons E (1994) Cecocolonic motility in the chicken. Effects of cholecystokinin. Life Sci 55(22): 1743–1755PubMedGoogle Scholar
  31. Stout JC, Weiss JM (1994) An animal model for measuring behavioral responses to anxiogenic and anxiolytic manipulation. Pharmacol Biochem Behav 47(3): 459–465PubMedGoogle Scholar
  32. Warsh JJ, Li PP (1996) Second messenger systems and mood disorders. Curr Opin Psychiatry 9: 23–29Google Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • H. Cohen
    • 1
  • M. Kotler
    • 1
  • Z. Kaplan
    • 1
  • M. A. Matar
    • 1
  • O. Kofman
    • 1
  • R. H. Belmaker
    • 1
  1. 1.Ministry of Health Mental Health Center, Faculty of Health SciencesBen Gurion University of the NegevBeershevaIsrael

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