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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
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: 99–102
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: 341–343
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: 1251–1260
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): 2279–2289
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 York
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: 1081–1086
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]: 428–429
Cohen H, Bar-Haim N, Kotler M (1996) Acute inositol induces anxiety in rats. Biol Psychiatry 40: 426–427
Crawley JN (1994) Interactions between cholecystokinin and other neurotransmitter systems. In: Bradwejn J (ed) Cholecystokinin and anxiety. From neuron to behavior. Biomédical Publishers, CRC Press
File SE (1993) The interplay of learning and anxiety in the elevated plus maze. Behav Brain Res 58(1–2): 199–202
Fux M, Levine J, Aviv A, Belmaker RH (1966) Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry 153: 1219–1221
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: 175–182
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: 139–147
Hallman M (1984) Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung. Biochim Biophys Acta 795: 67–78
Hallman M, Jarvenpaa AL, Pohjavuori (1986) Respiratory distress syndrome and inositol supplementation in preterm infants. Arch Dis Childhood 61: 1076–1083
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: 1233–1239
Jope RS, Williams MB (1994) Lithium and brain signal transduction systems. Biochem Pharmacol 47: 429–434
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: 558–567
Kofman O, Sherman WR, Katz V, Belmaker RH (1993) Restoration of brain myoinositol levels in rats increases latency to lithium-pilocarpine seizures. Psychopharmacology 110: 229–234
Kofman O, Belmaker RH (1993a) Biochemical, behavioral and clinical studies of the role of inositol in lithium treatment and depression. Biol Psychiatry 34: 839–852
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: 580–586
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: 487–490
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: 792–794
Levine J, Ring A, Barak Y, Elizur A, Belmaker RH (1995b) Inositol may worsen attention deficit disorder with hyperactivity. Hum Psychopharmacol 10: 481–484
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: 370–381
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: 73–75
Rahman S, Neuman RS (1993) Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization. Brain Res 631: 349–351
Ramos RT, Gentil V, Gorenstein C (1993) Clomipramine and initial worsening in panic disorder: beyond the “jitteriness syndrome”. J Psychopharmacol 7(3): 265–269
Reynolds JEF (1993) Martindale: the extra pharmacopoeia, 30th ed. The Pharmaceutical Press, London
Rodriguez SA, Martin MT, Fernandez E, Gonalons E (1994) Cecocolonic motility in the chicken. Effects of cholecystokinin. Life Sci 55(22): 1743–1755
Stout JC, Weiss JM (1994) An animal model for measuring behavioral responses to anxiogenic and anxiolytic manipulation. Pharmacol Biochem Behav 47(3): 459–465
Warsh JJ, Li PP (1996) Second messenger systems and mood disorders. Curr Opin Psychiatry 9: 23–29
About this article
Cite this article
Cohen, H., Kotler, M., Kaplan, Z. et al. Inositol has behavioral effects with adaptation after chronic administration. J. Neural Transmission 104, 299–305 (1997). https://doi.org/10.1007/BF01273190
- PI cycle
- animal model