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Pharmacopsychiatry 2000; 33(4): 132-137
DOI: 10.1055/s-2000-11220
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Acute Stress Induced Modifications of Calcium Signaling in Learned Helpless Rats

K. Velbinger1 , J. De Vry2 , K. Jentzsch2 , A. Eckert1, 3 , F. Henn1 , W. E. Müller1, 3
  • 1Central Institute of Mental Health, Departments of Psychopharmacology and Psychiatry, Mannheim, Germany
  • 2Troponwerke GmbH & Co. KG, Pharma Research CNS II, Cologne, Germany
  • 3Department of Pharmacology, Biocenter University of Frankfurt, Frankfurt/Main, Germany
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Publication History

03.09.1999

08.02.2000

Publication Date:
31 December 2000 (online)

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Previous reports have demonstrated reduced elevations of free intracellular calcium concentration in blood cells of depressed patients after various stimuli. Therefore, a disturbance of intracellular calcium (Ca2+) homeostasis has been postulated to be involved in the pathophysiology of mood disorders. It was the aim of the present study to investigate whether Ca2+ signaling was affected in spleen T-lymphocytes of rats submitted to a learned helplessness paradigm, an animal model of depression with a high level of construct, face and predictive validity. In addition, we tested for effects of acute stress on the Ca2+ signaling in helpless rats, as compared to non-stressed rats. It was found that mitogen-induced Ca2+ signaling only tended to be reduced in helpless rats. However, when helpless rats were submitted to acute immobilization stress, Ca2+ signaling appeared to be significantly blunted, whereas the same stressor did not affect Ca2+ signaling in the non-helpless control rats. These acute stress-induced differences in Ca2+ signaling were not paralleled by a differential increase in plasma corticosterone. It is hypothesized that blunted Ca2+ signaling, as assessed in spleen T-lymphocytes of helpless rats, may be a correlate of the increased vulnerability of helpless rats to acute stressors.

References

  • 1 Ackermann K D, Bellinger D L, Felten S Y, Felten D L. Ontogeny and senescence of noradrenergic innervation of the rodent thymus and spleen. In: Ader R, Cohen N, Felten DL (eds.) Psychoneuroimmunology. New York; Academic Press 1991: 71-125
    Google Scholar
  • 2 Aldenhoff J B, Dumais-Huber C, Fritzsche M, Sulger J, Vollmayr B. Altered Ca2+-homeostasis in single T-lymphocytes of depressed patients.  J. Psychiatr. Res.. 1997;  31 315-322
    CrossrefPubMedGoogle Scholar
  • 3 Bering B, Moises H W, Müller W E. Muscarinic cholinergic receptors on intact human lymphocytes. Properties and subclass characterization.  Biol. Psychiatry. 1987;  22 1451-1458
    CrossrefPubMedGoogle Scholar
  • 4 Bohus M, Förstner U, Kiefer C, Gebicke-Harter P, Timmer J, Spraul G, Wark H J, Hecht H, Berger M, van Calker D. Increased sensitivity of the inositol-phospholipid system in neutrophils from patients with acute major depressive episodes.  Psychiatry Res.. 1996;  65 45-51
    CrossrefPubMedGoogle Scholar
  • 5 Carman J S, Wyatt R J. Calcium: Bivalent cation in the bivalent psychoses.  Biol. Psychiatry. 1979;  14 295-336
    PubMedGoogle Scholar
  • 6 Cohen S, Herbert T B. Health Psychology: Psychological factors and physical disease from the perspective of human psychoneuroimmunology.  Annu. Rev. Psychol.. 1996;  47 113-142
    CrossrefPubMedGoogle Scholar
  • 7 Dantzer R, Kelley K W. Stress and immunity: An integrated view of relationships between the brain and the immune system.  Life Sci.. 1989;  44 195-2008
    PubMedGoogle Scholar
  • 8 De Vry J, Glaser T, Schuurman T, Schreiber R, Traber J. 5-HT1A receptors in anxiety. In: Briley M, File SE (eds.) New concepts in anxiety. London; MacMillan Press 1991: 94-129
    Google Scholar
  • 9 De Vry J, Fritze J, Post R M. The management of co-existing depression in patients with dementia: potential of calcium channel antagonists.  Clin. Neuropharmacol.. 1997;  20 22-35
    PubMedGoogle Scholar
  • 10 Dubovsky S L, Christiano J, Daniell L C, Murphy J, Adler L, Baker N, Harris A. Increased platelet intracellular calcium concentration in patiens with bipolar affective disorders.  Arch. Gen. Psychiatry. 1989;  46 632-638
    PubMedGoogle Scholar
  • 11 Dubovsky S L, Lee C, Christiano J, Murphy J. Elevated platelet intracellular calcium concentration in bipolar depression.  Biol. Psychiatry. 1991;  29 441-450
    CrossrefPubMedGoogle Scholar
  • 12 Dubovsky S L, Murphy J, Thomas M, Rademacher J. Abnormal intracellular calcium ion concentration in platelets and lymphocytes of bipolar patients.  Am. J. Psychiatry. 1992;  149 118-120
    PubMedGoogle Scholar
  • 13 Dubovsky S L, Franks R D. Intracellular calcium ions in affective disorders: A review and an hypothesis.  Biol. Psychiatry. 1993;  18 781-797
    PubMedGoogle Scholar
  • 14 Eckert A, Gann H, Riemann D, Aldenhoff J, Müller W E. Elevated intracellular calcium levels after 5-HT2 receptor stimulation in platelets of depressed patients.  Biol. Psychiatry. 1993;  34 565-568
    CrossrefPubMedGoogle Scholar
  • 15 Eckert A, Gann H, Riemann D, Aldenhoff J, Müller W E. Platelet and lymphocyte free intracellular calcium in affective disorders.  Eur. Arch. Psychiatry Clin. Neurosci.. 1994;  243 218-223
    PubMedGoogle Scholar
  • 16 Eckert A, Förstl H, Zerfass R, Hartmann H, Müller W E. Lymphocytes and neurophils as peripheral models to study the effect of β-amyloid on cellular calcium signaling in Alzheimer's disease.  Life Sci.. 1996;  59 499-510
    CrossrefPubMedGoogle Scholar
  • 18 Emamghoreishi M, Schlichter L, Li P P, Parikh S, Sen J, Kamble A, Warsh J J. High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder.  Am. J. Psychiatry. 1997;  154 976-982
    PubMedGoogle Scholar
  • 19 Giral P, Martin P, Soubrié P, Simon P. Reversal of helpless behaviour in rats by putative 5-HT1A agonists.  Biol. Psychiatry. 1988;  23 237-242
    CrossrefPubMedGoogle Scholar
  • 20 Grynkiewicz G, Poenie M, Tsien R Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties.  J. Biol. Chem.. 1985;  260 3440-3450
    PubMedGoogle Scholar
  • 21 Hartmann H, Eckert A, Förstl H, Müller W E. Similar age-related changes of free intracellular calcium in lymphocytes and central neurons: effects of Alzheimer's disease.  Eur. Arch. Psychiatry Clin. Neurosci.. 1994;  243 218-223
    PubMedGoogle Scholar
  • 22 Hartmann H, Velbinger K, Eckert A, Müller W E. Region-specific down-regulation of free intracellular calcium in the aged rat brain.  Neurobiol. Aging. 1996;  17 557-563
    CrossrefPubMedGoogle Scholar
  • 23 Helmeste D M, Tang S W. The role of calcium in the etiology of the affective disorders.  Jpn. J. Pharmacol.. 1998;  77 107-116
    CrossrefPubMedGoogle Scholar
  • 24 Henn F A, Johnson J, Edwards E, Anderson D. Melancholia in rodents: Neurobiology and pharmacology.  Psychopharmacol. Bull.. 1985;  21 443-445
    PubMedGoogle Scholar
  • 25 Henn F A, Edwards E, Muneyyirci J. Animal models of depression.  Clin. Neurosci.. 1993;  1 152-156
    PubMedGoogle Scholar
  • 26 Hough C, Lu S J, Davis C L, Chuang D M, Post R M. Elevated basal and thapsigargin-stimulated intracellular calcium of platelets and lymphocytes from bipolar affective disorder patients measured by a fluorometric microassay.  Biol. Psychiatry. 1999;  46 247-255
    CrossrefPubMedGoogle Scholar
  • 27 Irwin M, Daniels M, Bloom E T, Smith T L, Weiner H. Life events, depressive symptoms, and immune function.  Am. J. Psychiatry. 1987;  144 437-441
    PubMedGoogle Scholar
  • 28 Jesberger J A, Richardson J S. Animal models of depression: parallels and correlates to severe depression in humans.  Biol. Psychiatry. 1985;  20 764-784
    CrossrefPubMedGoogle Scholar
  • 29 Julius M H, Simpson E, Herzensberg L A. A rapid method for the isolation of functional thymus-derived murine lymphocytes.  Eur. J. Immunol.. 1973;  3 645-649
    CrossrefPubMedGoogle Scholar
  • 30 Kiecolt-Glaser J K, Glaser R. Psychoneuroimmunology and health consequences: Data and shared mechanisms.  Psychosom. Med.. 1995;  57 267-274
    PubMedGoogle Scholar
  • 31 Kubera M, Skowron-Cendrzak A, Mazur-Kolecka B, Bubak-Satora M, Basta-Kaim A, Laskowska-Bozek H, Ryzewski J. Stress-induced changes in muscarinic and β-adrenergic binding sites on rat thymocytes and lymphocytes.  J. Neuroimmunol.. 1992;  37 229-236
    CrossrefPubMedGoogle Scholar
  • 32 Kusumi I, Koyama T, Yamashita I. Serotonin stimulated Ca2+ response is increased in the blood platelets of depressed patients.  Biol. Psychiatry. 1991;  30 310-312
    CrossrefPubMedGoogle Scholar
  • 33 Kusumi I, Koyama T, Yamashita I. Thrombin-induced platelet calcium mobilization is enhanced in bipolar disorders.  Biol. Psychiatry. 1992;  32 731-734
    CrossrefPubMedGoogle Scholar
  • 34 Kusumi I, Koyama T, Yamashita I. Serotonin-induced platelet intracellular calcium mobilization in depressed patients.  Psychopharmacology. 1994;  113 322-327
    PubMedGoogle Scholar
  • 35 Laudenslager M L, Reite M, Harbeck R J. Suppressed immune response in infant monkeys associated with maternal separation.  Behav. Neural Biol.. 1982;  36 40-48
    PubMedGoogle Scholar
  • 36 Mikuni M, Kagaya A, Takahashi K, Meltzer H Y. Serotonin but not norepinephrine-induced calcium mobilization of platelets is enhanced in affective disorders.  Psychopharmacology. 1992;  106 311-314
    PubMedGoogle Scholar
  • 37 Moynihan J, Brenner G, Koota D, Breneman S, Cohen N, Ader R. Effects of handling on antibody production, mitogen responses, spleen cell number, and lymphocyte subpopulations.  Life Sci.. 1990;  46 1937-1944
    CrossrefPubMedGoogle Scholar
  • 38 Rabin B S, Cohen S, Ganguli R, Lysle D T, Cunnick J E. Bidirectional interaction between the central nervous system and the immune system.  Crit. Rev. Immunol.. 1989;  9 279-312
    PubMedGoogle Scholar
  • 39 Reite M, Harbeck R, Hoffmann A. Altered cellular immune response following peer separation.  Life Sci.. 1981;  29 1133-1136
    CrossrefPubMedGoogle Scholar
  • 40 Seligman M EP, Maier S F. Failure to escape traumatic shock.  J. Exp. Psychol.. 1967;  74 1-9
    PubMedGoogle Scholar
  • 41 Stein M, Miller A H, Trestman R L. Depression, the immune system, and health and illness.  Arch. Gen. Psychiatry. 1991;  48 171-177
    PubMedGoogle Scholar
  • 42 van Calker D, Förstner U, Bohus M, Gebicke-Harter P, Hecht H, Wark H J, Berger M. Increased sensitivity to agonist stimulation of the CA2+ response in neutrophils of manic-depressive patients: effect of lithium therapy.  Neuropsychobiology. 1993;  27 180-183
    PubMedGoogle Scholar
  • 43 Vescei P. Glucocorticoids: Cortisol, cortisone, corticosterone, compound S, and their metabolites. In: Jaffe BM, Behrman HR (eds.) Methods of hormone radioimmunoassay. New York, San Francisco, London; Academic Press 1979: 767-796
    Google Scholar
  • 44 Walker L G, Eremin O. Psychoneuroimmunology: A new fad or the fifth cancer treatment modality?.  Am. J. Surg.. 1995;  170 2-4
    CrossrefPubMedGoogle Scholar
  • 45 Willner P. Animal models of depression: An overview.  Pharmacol. Ther.. 1990;  45 425-455
    CrossrefPubMedGoogle Scholar
  • 46 Willner P, Muscat R, Papp M. Chronic mild stress-induced anhedonia: A realistic animal model of depression.  Neurosci. Biobehav. Rev.. 1992;  16 525-534
    CrossrefPubMedGoogle Scholar

Prof. Dr. W. E. Müller

Pharmakologisches Institut Biozentrum der Universität

Marie-Curie-Str. 9

60439 Frankfurt

Germany

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