, Volume 31, Issue 4, pp 305–320 | Cite as

The “isolation syndrome” in mice

  • L. Valzelli
Animal Studies


Isolation has been widely described to induce a strong aggressive behavior in many animal species and expecially in rodents.

However, a deeper analysis of such altered behavior induced by isolation, allows the identification, at least in mice, of several other changes involving numerous peripheral, behavioral and neurochemical functions, in such a way to debouch into a complex symptomatology. As a consequence of the manifold aspects involved in this experimental situation, the definition “isolation syndrome” seems to be much more adequate than the simplest definition of “aggressiveness by isolation”. On this frame work, some similarities with psychoneurosis in men are also suggested.

Key words

Isolation Syndrome Aggressiveness by Isolation Psychoneurosis Behavior Neurochemistry Neuroanatomy Psychotropic Drugs 


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  1. Adler, M. W.: Limbic lesion-induced changes in cerebral excitability. In: Drugs, development and cerebral functions, W. L. Smith, ed., pp. 167–176. Spring-field, Ill.: Ch. C. Thomas 1971.Google Scholar
  2. Allee, W. C.: Group organization among vertebrates. Science 95, 289–293 (1942).Google Scholar
  3. Anand, B. K., Dua, S.: Stimulation of limbic system of brain in waking animals. Science 122, 1139 (1955).Google Scholar
  4. Armitage, A. K., Hall, G. H.: Further evidence relating to the mode of action of nicotine in the central nervous system. Nature (Lond.) 214, 977–979 (1967).Google Scholar
  5. Bennett, E. L., Rosenzweig, M. R., Diamond, M. C.: Rat brain: effects of environmental enrichment on wet dry weights. Science 163, 825–826 (1969).Google Scholar
  6. Bennett, E. L., Rosenzweig, M. R., Diamond, M. C.: Time courses of effects of differential experience on brain measures and behavior of rats. In: Molecular approaches to learning and memory, W. L. Byrne, ed., pp. 55–89. New York: Academic Press 1970.Google Scholar
  7. Bittman, R., Essman, W. B.: 5-Hydroxytryptamine-nucleic acid interactions. Implications for physical and in vivo studies as a model for neural function. Paper, 3rd. Annual Winter Conference on Brain Research, Snowmass-at-Aspen, Colorado 1970.Google Scholar
  8. Blanchard, R. J., Blanchard, D. C.: Limbic lesions and reflexive fighting. J. comp. physiol. Psychol. 66, 603–605 (1968).Google Scholar
  9. Bohdanecky, Z., Jarvik, M. E.: Impairment of one-trial passive avoidance learning in mice by scopolamine, scopolamine methylbromide and physostigmine. Int. J. Neuropharmacol. 6, 217–222 (1967).Google Scholar
  10. Brodie, B. B., Costa, E., Dlabac, A., Neff, N. H., Smookler, H. H.: Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J. Pharmacol. exp. Ther. 154, 493–498 (1966).Google Scholar
  11. Buffery, A. W. H.: Learning and memory in baboons with bilateral lesions of frontal or inferotemporal cortex. Nature (Lond.) 214, 1054–1056 (1967).Google Scholar
  12. Charpentier, J.: Analysis and measurement of aggressive behaviour in mice. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 86–100. Amsterdam: Exerpta Medica 1969.Google Scholar
  13. Conner, R. L., Levine, S.: Hormonal influences on aggressive behaviour. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 150–163. Amsterdam: Excerpta Medica 1969.Google Scholar
  14. Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand. 62, Suppl. 232, 1–55 (1964a).Google Scholar
  15. Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta physiol. scand. 64, Suppl. 247 l-36 (1964b).Google Scholar
  16. Delgado, J. M. R.: Offensive-defensive behaviour in free monkeys and chimpazees induced by radio stimulation of the brain. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 109–119. Amsterdam: Excerpta Medica 1969.Google Scholar
  17. Denenberg, V. H., Morton, J. R., Haltmeyer, G. C.: Effect of social grouping upon emotional behaviour. Anim. Behav. 12, 205–208 (1964).Google Scholar
  18. Deutsch, J. A., Lutzky, H.: Memory enhancement by anticholinesterase as a function of initial learning. Nature (Lond.) 213, 742 (1967).Google Scholar
  19. Diamond, M. C., Krech, D., Rosenzweig, M. R.: The effects of an enriched environment on the histology of the rat cerebral cortex. J. comp. Neurol. 123, 111–120 (1964).Google Scholar
  20. Diamond, M. C., Law, F., Rhodes, H., Lindner, B., Rosenzweig, M. R., Krech, D., Bennett, E. L.: Increases in cortical depth and glia numbers in rats subjected to enriched environment. J. comp. Neurol. 128, 117–126 (1966).Google Scholar
  21. Egger, M. D., Flynn, J. P.: Further studies on the effects of amygdaloid stimulation and ablation on hypothalamically elicited attack behaviour in cats. In: Progress in brain research, vol. 27, Structure and function of the limbic system, W. R. Adey and T. Tokizane, eds., pp. 165–182. Amsterdam: Elsevier 1967.Google Scholar
  22. Essman, W. B.: The development of activity differences in isolated and aggregated mice. Anim. Behav. 4, 406–409 (1966).Google Scholar
  23. Essman, W. B.: Differences in locomotor activity and brain-serotonin metabolism in differentially housed mice. J. comp. physiol. Psychol. 66, 244–246 (1968).Google Scholar
  24. Essman, W. B.: “Free” and motivated behaviour and amine metabolism in isolated mice. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 203–208. Amsterdam: Excerpta Medica 1969.Google Scholar
  25. Essman, W. B.: Some neurochemical correlates of altered memory consolidation. Trans. N.Y. Acad. Sci. 32, 948–973 (1970).Google Scholar
  26. Essman, W. B.: Drug effects and learning and memory processes. Advanc. Pharmacol. Chemother. 9, 241–330 (1971a).Google Scholar
  27. Essman, W. B.: Neurochemical changes associated with isolation and environmental stimulation. Biol. Psychiat. 3, 141–147 (1971b).Google Scholar
  28. Essman, W. B.: Metabolic and behavioral consequences of nicotine. In: Drugs, development and cerebral functions. W. L. Smith, ed. Springfield, Ill.: Ch. C. Thomas 1971c.Google Scholar
  29. Essman, W. B.: Changes in cholinergic activity and avoidance behavior by nicotine in differentially housed mice. Int. J. Neurosci. 2, 199–206 (1971d).Google Scholar
  30. Essman, W. B.: Contributions of differential housing to brain development: some implications for sleep behavior. In: Sleep and the maturing nervous system, C. D. Clemente, D. P. Purpura and F. E. Mayer, eds., pp. 99–107. New York: Academic Press 1972.Google Scholar
  31. Essman, W. B., Essman, S. G.: Enhanced memory consolidation with drug-induced regional changes in brain RNA and serotonin metabolism. Pharmako-psychiat. Neuropsychopharmacol. 2, 28–34 (1969).Google Scholar
  32. Essman, W. B., Essman, S. G.: Cholinergic mechanisms and avoidance behavior acquisition: effects of nicotine in mice. Psychol. Rep. 29, 987–993 (1971).Google Scholar
  33. Essman, W. B., Frisone, J. F.: Isolation-induced facilitation of gastric ulcerogenesis. J. Psychosom. Res. 10, 183–188 (1966).Google Scholar
  34. Essman, W. B., Heldman, E., Barker, L. A., Valzelli, L.: Development of microsomal changes in liver and brain of differentially housed mice. Fed. Proc. 31, 121 (1972).Google Scholar
  35. Ferchmin, P. A., Eterovic, V. A., Caputto, R.: Studies on brain weight and RNA content after short periods of exposure to environmental complexity. Brain Res. 20, 49–57 (1970).Google Scholar
  36. Fiske, D. W., Maddi, S. R.: Functions of varied experience. Homewood, Ill.: Dorsey 1961.Google Scholar
  37. Fonberg, E.: Effect of partial destruction of the amygdaloid complex on the emotional-defensive behavior of dogs. Bull. Acad. pol. Sci. 13, 429–432 (1965).Google Scholar
  38. Forgays, D. G., Forgays, J. W.: The nature of the effects of free environmental experience in the rat. J. comp. physiol. Psychol. 45, 322–328 (1952).Google Scholar
  39. Fuxe, K.: Distribution of monoamine nerve terminals in the central nervous system. Acta physiol. scand. 64, Suppl. 247, 37–86 (1964).Google Scholar
  40. Garattini, S., Giacalone, E., Valzelli, L.: Biochemical changes during isolation-induced aggressiveness in mice. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 179–187. Amsterdam: Excerpta Medica 1969.Google Scholar
  41. Gumulka, W., Samanin, R., Valzelli, L.: Effect of chlorpromazine on 5-hydroxytryptamine metabolism in hippocampal stimulated rats. Europ. J. Pharmacol. 12, 276–279 (1970).Google Scholar
  42. Henry, J. P., Meehan, J. P., Stephens, P. M.: The use of psychosocial stimuli to induce prolonged systolic hypertension in mice. Psychosom. Med. 29, 408–432 (1967).Google Scholar
  43. Horvath, F. E.: Effects of basolateral amygdalectomy on three types of avoidance behavior in cats. J. comp. physiol. Psychol. 56, 380–389 (1963).Google Scholar
  44. Hymovitch, B.: The effects of environmental variations on problem solving in the rat. J. comp. physiol. Psychol. 45, 313–321 (1952).Google Scholar
  45. Kaada, B. R., Andersen, P., Jansen, J., Jr.: Stimulation of the amygdaloid nuclear complex in unanesthetized cats. Neurology (Minneap.) 4, 48–64 (1954).Google Scholar
  46. Karczmar, A. G., Scudder, C. L.: Aggression and neurochemical changes in different strains and genera on mice. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 209–227. Amsterdam: Excerpta Medica 1969.Google Scholar
  47. Karli, P., Vergnes, M.: Déclenchement du comportement d'agression interspécifique rat-souris par des lésions expérimentales des la bandelette olfactive latérale et du cortex prépyriforme. C. R. Soc. Biol. (Paris) 157, 372–374 (1963).Google Scholar
  48. Kety, S. S.: The biogenic amines in emotion and arousal. In: The Neurosciences: second study program, F. O. Schmitt, ed., pp. 324–336. New York: Rockfeller University Press 1970.Google Scholar
  49. Kling, A.: Behavioral and somatic development following lesions of the amygdala in the cat. J. psychiat. Res. 3, 263–273 (1965).Google Scholar
  50. Kling, A.: Effects of amygdalectomy and testosterone on sexual behavior of male juvenile macaques. J. comp. physiol. Psychol. 65, 466–471 (1968).Google Scholar
  51. Kluver, H., Bucy, P. C.: Preliminary analysis of functions of the temporal lobes in monkeys. Arch. Neurol. Psychiat. (Chic.) 42, 979–1000 (1939).Google Scholar
  52. Krech, D., Rosenzweig, M. R., Bennett, E. L.: Relations between brain chemistry and problem-solving among rats raised in enriched and impoverished environments. J. comp. physiol. Psychiol. 55, 801–807 (1962).Google Scholar
  53. Kršiak, M., Janků, I.: The development of aggressive behaviour in mice by isolation. In: Aggressive behaviour, S. Garattini, and E. B. Sigg, eds., pp. 101–105. Amsterdam: Excerpta Medica 1969.Google Scholar
  54. Lagerspetz, K. M. J.: Aggression and aggressiveness in laboratory mice. In: Aggressive Behaviour, S. Garattini and E. B. Sigg, eds., pp. 77–85. Amsterdam: Excerpta Medica 1969.Google Scholar
  55. Leaf, R. C., Muller, S. A.: Effect of scopolamine on operant avoidance acquisition and retention. Psychopharmacologia (Berl.) 9, 10–11 (1966).Google Scholar
  56. Leff, J. P.: Perceptual phenomena and personality in sensory deprivation. Brit. J. Psychiat. 114, 1499–1508 (1968).Google Scholar
  57. Marcucci, F., Mussini, E., Valzelli, L., Garattini, S.: Decrease in N-acetyl-L-aspartic acid in brain of aggressive mice. J. Neurochem. 15, 53–54 (1968).Google Scholar
  58. Miller, N. E., Dollard, J.: Social learning and imitation. New Haven: Yacke University Press 1941.Google Scholar
  59. Miller, S. C.: Ego-anatomy in sensory deprivation, isolation and stress. Int. J. Psycho-Anal. 43, 1–20 (1962).Google Scholar
  60. Moyer, K. E.: Kinds of aggression and their physiological basis. Commun. Behav. Biol. 2, pt. A, 65–87 (1968).Google Scholar
  61. Ojemann, R. G.: Correlations between specific human brain lesions and memory changes. Neurosci. Res. Progr. Bull. 4, Suppl., 1–70 (1966).Google Scholar
  62. Osgood, C. E.: Method and theory in experimental psychology. New York: University Press 1953.Google Scholar
  63. Pallaud, B.: Mise en evidence d'un comportement d'imitation chez la souris. Rév. Comp. Animal (1968).Google Scholar
  64. Pallaud, B.: Influence d'un congénère sur l'apprentissage chez la souris. C. R. Acad. Sci. (Paris) 268, 118–120 (1969a).Google Scholar
  65. Pallaud, B.: Influence d'un congénère sur la performance chez la souris. C. R. Acad. Sci. (Paris) 269, 1101–1104 (1969b).Google Scholar
  66. Pollard, J. C., Uhr, L., Jackson, C. W.: Studies in sensory deprivation. Arch. gen. Psychiat. 8, 435–454 (1963).Google Scholar
  67. Reis, D. J., Gunne, L. M.: Brain catecholamines: relation to the defense reaction evoked by amygdaloid stimulation in cat. Science 149, 450–451 (1965).Google Scholar
  68. Robinson, E.: Effect of amygdalectomy on fear-motivated behavior in rats. J. comp. physiol. Psychol. 56, 814–820 (1963).Google Scholar
  69. Rosenzweig, M. R.: Effects of heredity and environment on brain chemistry, brain anatomy and learning ability in the rat. Symposium on physiological derminates of behavior: implications for mental retardation. Kans. Study Educ. 14, 3–34 (1964).Google Scholar
  70. Rosenzweig, M. R.: Environmental complexity, cerebral change and behavior. Amer. Psychol. 21, 321–332 (1966).Google Scholar
  71. Rosenzweig, M. R., Bennett, E. L., Diamond, M. C., Wu, S., Slange, R. W., Saffran, E.: Influences of environmental complexity and visual stimulation on development of occipital cortex in rat. Brain Res. 14, 427–445 (1969).Google Scholar
  72. Rosenzweig, M. R., Love, W., Bennett, E. L.: Effects of a few hours a day of enriched experience on brain chemistry and brain weights. Physiol. Behav. 3 819–825 (1968).Google Scholar
  73. Rosenzweig, N.: Sensory deprivation and schizophrenia: some clinical and theoretical similarities. Amer. J. Psychiat. 116, 326–329 (1959).Google Scholar
  74. Rosenzweig, N., Gardner, L. M.: The role of input relevance in sensory isolation. Amer. J. Psychol. 122, 920–928 (1966).Google Scholar
  75. Russell, R. W., Watson, R. H. J., Frankenaeuser, M.: Effects of chronic reductions in brain cholinesterase activity on acquisition and extinction of a conditioned avoidance response. Scand. J. Psychol. 2, 21–29 (1961).Google Scholar
  76. Scott, J. P.: Aggression. Chicago: University of Chicago Press 1959.Google Scholar
  77. Seward, J. P.: Aggressive behavior in the rat. IV. Submission as determined by conditioning, extinction, and disease. J. comp. Psychol. 39, 51–75 (1946).Google Scholar
  78. Sigg, E. B.: Relationship of aggressive behavior to adrenal and gonadal function in male mice. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 143–149. Amsterdam: Excerpta Medica 1969.Google Scholar
  79. Solokov, E. N.: Higher nervous functions; the orienting reflex. Ann. Rev. Physiol. 25, 545–580 (1963).Google Scholar
  80. Tenen, S. S.: The effects of p-chlorophenylalanine, a serotonin depletor, on avoidance acquisition, pain sensitivity and related behavior in the rat. Psychopharmacologia (Berl.) 10, 204–219 (1967).Google Scholar
  81. Tozer, T. N., Neff, N. H., Brodie, B. B.: Application of steady state kinetics to the synthesis rate and turnover time of serotonin in the brain of normal and reserpine treated rats. J. Pharmacol. exp. Ther. 153, 177–182 (1966).Google Scholar
  82. Valzelli, L.: Drugs and aggressiveness. Advanc. Pharmacol. 5, 79–108 (1967a).Google Scholar
  83. Valzelli, L.: Biological and pharmacological aspects of aggressiveness in mice. In: Neuropsychopharmacology. Proc. 5th Int. CINP Congress, Washington, 1966, H. Brill, ed., pp. 28–31. Amsterdam: Excerpta Medica 1967b.Google Scholar
  84. Valzelli, L.: Aggressive behaviour induced by isolation. In: Aggressive Behaviour, S. Garattini and E. B. Sigg, eds., pp. 70–76. Amsterdam: Excerpta Medica 1969a.Google Scholar
  85. Valzelli, L.: The exploratory behaviour in normal and aggressive mice. Psychopharmacologia (Berl.) 15, 232–235 (1969b).Google Scholar
  86. Valzelli, L.: Agressivité chez le rat et la souris: aspects comportementaux et biochimiques. Actualités pharmacol. 24, 133–152 (1971a).Google Scholar
  87. Valzelli. L.: Further aspects of the exploratory behavior in aggressive mice. Psychopharmacologia (Berl.) 19, 91–94 (1971b).Google Scholar
  88. Valzelli, L.: Profili di psicofisiologia e neurochimica Milano: Manfredi Publ. 1972.Google Scholar
  89. Valzelli, L.: Activity of benzodiazepines on aggressive behavor in rats and mice. In: The benzodiazepines, S. Garattini, E. Mussini and L.O. Randall,eds., pp. 405–417. New York: Raven Press 1973a.Google Scholar
  90. Valzelli, L.: Psychopharmacology: an introduction to experimental and clinical principles. New York: Spectrum Publ. 1973b.Google Scholar
  91. Valzelli, L., Bernasconi, S.: Differential activity of some psychotropic drugs as a function of emotional level in animals. Psychopharmacologia (Berl.) 20, 91–96 (1971).Google Scholar
  92. Valzelli, L., Ghezzi, D., Bernasconi, S.: Benzodiazepine activity on some aspects of behavior. Totus Homo 3, 73–79 (1971).Google Scholar
  93. Valzelli, L., Giacalone, E., Garattini, S.: Pharmacological control of aggressive behavior in mice. Europ. J. Pharmacol. 2, 144–146 (1967).Google Scholar
  94. Vergnes, M., Karli, P.: Effets de lésions expérimentales du néocortex frontal et du noyau caudé sur l'agressivité interspécifique rat-souris. C. R. Soc. Biol. (Paris) 157, 176–178 (1963).Google Scholar
  95. Vergnes, M., Karli, P.: Effets de la stimulation de l'hypothalamus latéral de l'amygdale et de l'ippocampe sur le comportement d'agression interspécifique ratsouris. Physiol. Behav. 4, 889–894 (1969).Google Scholar
  96. Weiskrantz, L.: Behavioral changes associated with ablation of the amygdaloid complex in monkeys. J. comp. physiol. Psychol. 49, 381–391 (1956).Google Scholar
  97. Welch, A. S., Welch, B. L.: Isolation, reactivity and aggression: evidence for an involvement of brain catecholamines and serotonin. In: The physiology of aggression and defeat, B. E. Eleftheriou and J. P. Scott, eds., pp. 91–142. New York: Plenum Press 1971.Google Scholar
  98. Welch, B. L.: Psychophysiological response to the mean level of environmental stimulation: a theory of environmental integration. In: Symposium of the medical aspects of stress in the military climate, D. Mck. Rioch, ed., pp. 39–96. Washington: U.S. Government Printing Office 1965.Google Scholar
  99. Welch, B. L., Welch, A. S.: Aggression and the biogenic amine neurohumors. In: Aggressive behaviour, S. Garattini and E. B. Sigg, eds., pp. 188–202. Amsterdam: Excerpta Medica 1969.Google Scholar
  100. Woolley, D. W.: A method for the demonstration of the effects of serotonin on learning ability. In: Pharmacology of conditioning, learning and retention, M.Ya. Mikhel'son and V. G. Longo, eds., pp. 231–236. Oxford: Pergamon Press 1965.Google Scholar
  101. Yen, C. Y., Stanger, L., Millman, N.: Ataractic suppression of isolation-induced aggressive behavior. Arch. int. Pharmacodyn. 123, 179–185 (1959).Google Scholar

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© Springer-Verlag 1973

Authors and Affiliations

  • L. Valzelli
    • 1
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri“MilanoItaly

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