Research Article| Volume 22, ISSUE 7, P892-898, July 1987

Alterations by antidepressants of cerebrospinal fluid formation and calcium distribution dynamics in the intact rat brain

  • Amiram I. Barkai
    Address reprint requests to Dr. Amiram I. Barkai, Department of Psychiatry, Columbia University College of Physicians and Surgeons, 722 W. 168th Street, New York, NY 10032.
    New York State Psychiatric Institute and the Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NYU.S.A.
    Search for articles by this author
  • Henry D. Nelson
    New York State Psychiatric Institute and the Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NYU.S.A.
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      The formation of cerebrospinal fluid (CSF) after chronic treatment with imipramine (IMI), lithium (Li), or electroshock (EST) was studied in urethane-anesthetized rats by ventricular-cisternal perfusion with 14C-inulin. Effects of these treatments on the removal of 45Ca from the cerebroventricular perfusate were also studied. The mean value for CSF formation in control rats was 2.6 ± 0.2μ/min. EST and IMI both increased CSF formation significantly ( + 38% and +19%, respectively). Li caused a significant decrease ( − 19%). Endogenous removal of 45Ca was by bulk CSF absorption to blood and by uptake to brain. In control animals, the uptake by brain accounted for 42% of the total endogenous removal at the steady state. Each of the applied treatments resulted in a significant decrease in the fraction of 45Ca taken up by the brain (EST 26%, IMI 33%, Li 29%). Thus, although chronic EST or IMI resulted in an effect opposite to that obtained by Li on CSF formation, all three treatments appear to act similarly in reducing calcium passage from the cerebroventricular compartment to brain tissue.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Aird RB
        • Becker RA
        The blood brain barrier in clinical disease: A review.
        J Nerv Ment Dis. 1963; 136: 517-526
        • Angel C
        • Roberts AJ
        Effects of electroshock and antidepressant drugs on cerebrovascular permeability to cocaine in the rat.
        J Nerv Ment Dis. 1966; 142: 376-380
        • Arato M
        • Rihmer Z
        • Felszeghy K
        Reduced plasma C-AMP level during prophylactic lithium treatment in patients with affective disorders.
        Biol Psychiatry. 1980; 15: 319-322
        • Barkai AI
        Myo-inositol turnover in the intact rat brain: Increased production after d-amphetamine.
        J Neurochem. 1981; 36: 1485-1491
        • Barkai AI
        Long-term effect of electroshock treatment on the entry of calcium into the cerebroventricular fluid in the rat.
        J Neurosci Res. 1983; 9: 165-171
        • Barkai AI
        • Meltzer HL
        Regulation of calcium entry into the extracellular environment of the rat brain.
        J Neurosci. 1982; 2: 1322-1328
        • Bech P
        • Kirkegaard C
        • Bock E
        • Johannesen M
        • Rafaelsen OJ
        Hornous, electrolytes and cerebrospinal fluid proteins in manic-melancholic patients.
        Neuropsychobiology. 1978; 4: 99
        • Belmaker RH
        Receptors, adenylate cyclase depression and lithium.
        Biol Psychiatry. 1981; 16: 333-350
        • Bjerner B
        • Borman T
        • Swensson A
        Tierexperimintalk untersuchumgen uber Schadigungen der Gefasse mit Permeabilitatsstorumgen und Bluntgen im Gehirm bei Electroshock behund Lung.
        Acta Psychiatr Neurol Scand. 1944; 19: 431-452
        • Carman JS
        • Post RM
        • Goodwin FK
        • Bunney Jr, WE
        Calcium and electroconvulsive therapy of severe depressive illness.
        Biol Psychiatry. 1977; 12: 5-18
        • Coppen A
        Abnormality of the blood CSF barrier of patients suffering from a depressive illness.
        J Neurol Neurosurg Psychiatry. 1960; 23: 156-161
        • Cserr H
        Potassium exchange between CSF plasma and brain.
        Am J Physiol. 1965; 209: 1219-1226
        • Cserr H
        Physiology of the choroid plexus.
        Physiol Rev. 1971; 51: 273-311
        • Edvinsson L
        • Nielsen KC
        • Owman C
        Innervation of choroid plexus in rabbits and cats.
        Brain Res. 1973; 63: 500-503
        • Frazer A
        • Haugaard ES
        • Mendels J
        • Haugaard M
        Effects of intracellular lithium on epinephrine-induced accumulation of C-AMP in skeletal muscle.
        Biochem Pharmacol. 1975; 24: 2273-2277
        • Hay wood JR
        • Vogh BP
        Some measurements of autonomic nervous system influence on production of cerbrospinal fluid.
        J Pharmacol Exp Ther. 1979; 208: 341-346
        • Heisey SR
        • Held D
        • Pappenheimer JR
        Bulk flow and diffusion in the cerebrospinal fluid system of the goat.
        Am J Physiol. 1962; 203: 775-781
        • Jimerson DC
        • Post RM
        • Carman JS
        • VanKammen DP
        • Wood JH
        • Goodwin FK
        • Bunney Jr, WE
        CSF calcium: Clinical correlates in affective illness and schizophrenia.
        Biol Psychiatry. 1979; 14: 37-51
        • Kent TA
        • Preskorn SH
        • Glotzbach RK
        • Irwin GH
        Amitriptyline normalizes tetrabenazine-induced changes in cerebral microcirculation.
        Biol Psychiatry. 1986; 21: 483-491
        • Lerer B
        • Stanley M
        • Belmaker RH
        ECT and lithium: Parallels and contrasts in receptor mechanisms.
        in: Lerer B Weiner RD Belmaker RD ECT: Basic Mechanisms. John Libbcy, London1984
        • Lindvall M
        • Edvinsson L
        • Owman C
        Sympathetic nervous control of CSF production from the choroid plexus.
        Science. 1978; 201: 176-178
        • Meltzer HL
        Lithium mechanisms in bipolar illness and altered intracellular calcium functions.
        Biol Psychiatry. 1986; 21: 492-510
        • Newman M
        • Ehud-Klein BM
        • Feinsod M
        • Belmaker RH
        Lithium at therapeutic concentrations inhibits brain noradrenaline-sensitive cyclic AMP accumulation.
        Brain Res. 1983; 278: 380-381
        • Preskorn SH
        • Irwin GH
        • Simpson S
        • Friesen D
        • Rinne J
        • Jerkovich G
        Medical therapies for mood disorders alter the blood-brain barrier.
        Science. 1981; 213: 469-471
        • Preskorn SH
        • Kent TA
        • Glotzbach R
        • Irwin GH
        • Solnick JV
        Cerebromicrocirculatory defects in a model of depression.
        Psychopharmacology. 1984; 84: 169-199
        • Sulser F
        • Janowsky AJ
        • Okada F
        • Manier DH
        • Mobley PL
        Regulation of recognition and action function of the NE receptor-coupled adenylate cyclase system in the brain: Implications for the therapy of depression.
        Neuropharmacology. 1983; 22: 425-431
        • Wright EM
        Transport processes in the formation of CSF.
        Rev Physiol Biochem Pharmacol. 1978; 83: 1-34