Effects of haloperidol, lithium, and valproate on phosphoinositide turnover in rat brain

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Abstract

The effects of acute, subacute, and chronic treatment with haloperidol, lithium, and valproate on inositol phosphate (IP) formation were examined. Acute treatment with haloperidol or the combination of haloperidol and lithium significantly reduced IP basal cortical levels. Subacute (three days) treatment with lithium decreased the IP basal level in the frontal cortex. Chronic treatment with haloperidol (14 and 28 days) caused a significant attenuation of carbachol-sensitive IP accumulation in the frontal cortex and striatum and a significant decrease in norepinephrine (NE)-induced IP formation in the frontal cortex (14 and 28 days) and striatum (28 days). Lithium treatment for 14 days produced a significant reduction in the IP basal cortical value, and a significant reduction in cortical carbachol- and NE-induced IP formation was found after 28 days of lithium treatment. The combination of haloperidol and lithium for 28 days decreased the striatal carbachol- and cortical NE-induced IP accumulation and caused a significant increase in NE-sensitive IP formation in the striatum at 14 days. Valproate treatment for 28 days was associated with a significant attenuation in striatal agonist-stimulated IP formation. Therefore, three drugs with different specificities for primary neurotransmitters may have common effects on second-messenger systems.

References (38)

  • M. Pizzi et al.

    Dopamine D2 receptor stimulation decreases the inositol trisphosphate level of rat striatal slices

    Eur. J. Pharmacol.

    (1987)
  • S. Puzynski et al.

    Valproic acid amide in the treatment of affective and schizoaffective disorders

    J. Affective Disord.

    (1984)
  • G. Schreiber et al.

    Lithium-selective alteration of the function of brain vs. cardiac Gs protein

    Neuropharmacology

    (1990)
  • J.H. Allison et al.

    Reduced brain inositol in lithium treated rats

    Nature (Lond.)

    (1971)
  • S. Avissar et al.

    Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex

    Nature

    (1988)
  • J.M. Baraban et al.

    Second messenger systems and psychoactive drug action: Focus on the phosphoinositide system andlithium

    Am. J. Psychiatry

    (1989)
  • R. Bersford et al.

    Haloperidol decanoate

    Drugs

    (1987)
  • M.J. Berridge et al.

    Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands

    Biochem. J.

    (1982)
  • R. Brown

    U.S. experience with valproate in manic depressive illness: A multicenter trial

    J. Clin. Psychiatry

    (1989)
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