Neuroscience and Behavioral Physiology

, Volume 33, Issue 1, pp 13–29 | Cite as

Influence of Postweaning Social Isolation in the Rat on Brain Development, Conditioned Behavior, and Neurotransmission

  • M. D. S. Lapiz
  • A. Fulford
  • S. Muchimapura
  • R. Mason
  • T. Parker
  • C. A. Marsden
Article

Abstract

There is substantial evidence that early life events influence brain development and subsequent adult behavior and play an important role in the causation of certain psychiatric disorders including schizophrenia and depression. The underlying mechanism of the effects of these early environmental factors is still not understood. It is a challenge to attempt to model early environmental factors in animals to gain understanding of the basic mechanisms that underlie the long-term effects. This paper reviews the effects of rearing rats from weaning in social isolation and reports some recent results indicating hippocampal dysfunction.

Isolation rearing in rats from weaning produces a range of persistent behavioral changes in the young adult, including hyperactivity in response to novelty and amphetamine and altered responses to conditioning. These are associated with alterations in the central aminergic neurotransmitter functions in the mesolimbic areas and other brain regions. Isolation-reared rats have enhanced presynaptic dopamine (DA) and 5-HT function in the nucleus accumbens (NAC) associated with decreased presynaptic 5-HT function in the frontal cortex and hippocampus. Isolation-reared rats have reduced presynaptic noradrenergic function in the hippocampus, but have enhanced presynaptic DA function in the amygdala. These neurochemical imbalances may contribute to the exaggerated response of the isolated rat to a novel stimulus or to stimuli predictive of danger, and isolation-induced behavioral changes. These changes have neuroanatomical correlates, changes which seem to parallel to a certain degree those seen in human schizophrenia. A greater understanding of the processes that underlie these changes should improve our knowledge of how environmental events may alter brain development and function, and play a role in the development of neuropsychiatric disorders.

social isolation conditioned behavior hippocampal dysfunction rat 

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REFERENCES

  1. 1.
    J. Altman and G. D. Das, “Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in the rat.” J. Comp. Neurol., No. 124, 319–336 (1965).Google Scholar
  2. 2.
    C. Beaulieu and M. Colonnier, “Richness of environment affects the number of contacts formed by buotons containing flat vesicles but does not alter the number of these boutons per neuron,” J. Comp. Neurol., No. 274, 347–356 (1988).Google Scholar
  3. 3.
    M. J. Bickerdicke, I. K. Wright, and C. A. Marsden, “Social isolation attenuates rat forebrain 5-HT release induced by KCl stimulation and exposure to a novel environment,” Behav. Pharmacol., No. 4, 231–236 (1993).Google Scholar
  4. 4.
    M. E. Bitterman, “The evolution of intelligence,” Scientific American, No. 212, 92–100 (1965).Google Scholar
  5. 5.
    S. L. Bowling, J. K. Rowlett, and M. T. Bardo, “The effect of environmental enrichment on amphetamine-stimulated locomotor activity, dopamine synthesis and dopamine release,” Neuropharmacology, No. 32, 885–893. (1993).Google Scholar
  6. 6.
    D. L. Braff and M. A. Geyer, “Sensorimotor gating and schizophrenia: human and animal model studies,” Arch. Gen. Psychiatry, No. 47, 181–188 (1990).Google Scholar
  7. 7.
    D. L. Braff, C. Grillon, and M. A. Geyer, “Gating and habituation of the startle reflex in schizophrenic patients,” Arch. Gen. Psychiatry, No. 49, 206–215 (1992).Google Scholar
  8. 8.
    D. L. Braff, C. Stone, E. Callaway, M. A. Geyer, I. D. Glick, and L. Bali, “Prestimulus effects of human startle reflex in normals and schizophrenics,” Psychophysiol., No. 15, 339–343 (1978).Google Scholar
  9. 9.
    A. K. Cadogan, D. A. Kendall, and C. A. Marsden, “Serotonin 5-HT(1A) receptor activation increases cyclic AMP formation in the rat hippocampus in vivo,” J. Neurochem., No. 62, 1816–1821 (1994).Google Scholar
  10. 10.
    J. T. Coyle and D. Henry, “Catecholamines in foetal and newborn rat brain,” J. Neurochem., No. 21, 61–67. 1973.Google Scholar
  11. 11.
    M. C. Diamond, “Extensive cortical depth measurements and neuronal size increases in the cortex of environmental enriched rats,” J. Comp. Neurol., No. 131, 357–364 (1967).Google Scholar
  12. 12.
    M. C. Diamond, F. Law, H. Rhodes, B. Lindner, M. R. Rosenzweig, D. Krech, and E. L. Bennett, “Increases in cortical depth and glia number in rats subjected to rich environment,” J. Comp. Neurol., No. 128, 117–126 (1966).Google Scholar
  13. 13.
    M. C. Diamond, B. Linder, R. Johnson, E. L. Bennett, and M. R. Rosenzweig, “Differences in occipital cortical synapses from environmentally enriched, impoverished and standard colony rats,” J Neurosci. Res., No. 1, 109–119 (1975).Google Scholar
  14. 14.
    L. P. Dwoskin, G. A. Gerhardt, C. J. Drebing, C. C. Wilcox, and N. R. Zahniser, “Uptake and release of dopamine from rat striatal slices: Comparison of PCP, amphetamine and nomifensine,” in: P. M. Beart, G. N. Woodruff, and D. M. Jackson (eds.), Pharmacology and Functional Regulation of Dopamine Neurons (1988).Google Scholar
  15. 15.
    S. L. Eastwood and P. J. Harrison, “Detection and quantification of hippocampal synaptophysin messenger RNA in schizophrenia using autoclaves, formalin-fixed, paraffin wax-embedded sections,” Neuroscience, No. 93, 99–106 (1999).Google Scholar
  16. 16.
    S. L. Eastwood, P. W. J. Burnet, and P. J. Harrison, “Altered synaptophysin expression as a marker of synaptic pathology in schizophrenia,” Neuroscience, No. 66, 309–319 (1995).Google Scholar
  17. 17.
    D. Einon and B. J. Sahakian, “Environmentally induced differences in susceptibility of rats to CNS stimulants and CNS depressants: evidence against a unitary explanation,” Psychopharmacology, No. 61, 299–307 (1979).Google Scholar
  18. 18.
    D. F. Einon, “Spatial memory and response strategies in rats: age, sex and rearing differences in performance,” Quart. J. Exper. Psychol., No. 32, 473–489 (1980).Google Scholar
  19. 19.
    D. F. Einon, A. P. Humphreys, S. M. Chivers, S. Field, and V. Naylor, “Isolation has permanent effects upon the behavior of the rat, but not the mouse, gerbil or guinea pig,” Dev. Psychobiol., No. 14, 343–355 (1980).Google Scholar
  20. 20.
    D. F. Einon and M. J. Morgan, “A critical period for social isolation in the rat,” Dev. Psychobiol., No. 10, 123–132 (1977).Google Scholar
  21. 21.
    B. F. M. Fiala, F. M. Snow, and W. T. Greenough, “'Impoverished' rats weigh more than 'enriched' rats because they eat more,” Dev. Psychobiol., No. 10, 537–541 (1977).Google Scholar
  22. 22.
    M. K. Floeter and W. T. Greenough, “Cerebellar plasticity: modification of Purkinje cell structure by differential rearing in monkeys,” Science, No. 206, 227–229 (1979).Google Scholar
  23. 23.
    K. C. F. Fone, K. Shalders, Z. D. Fox, R. Arthur, and C. A. Marsden, “Increased 5-HT2C receptor responsiveness occurs on rearing rats in social isolation,” Psychopharmacology, No. 123, 346–352 (1996).Google Scholar
  24. 24.
    A. J. Fulford, S. Butler, D. J. Heal, D. A. Kendall, and C. A. Marsden, “Evidence of altered α2-adrenoceptor function following isolation-rearing in the rat,” Psychopharmacology, No. 116, 183–190 (1994).Google Scholar
  25. 25.
    A. J. Fulford and C. A. Marsden, “Conditioned release of 5-hydroxytryptamine in vivo in the nucleus accumbens following isolation-rearing in the rat,” Neuroscience, No. 83, 481–487 (1997).Google Scholar
  26. 26.
    A. J. Fulford and C. A. Marsden, “Effect of isolation-rearing on conditioned dopamine release in vivo in the nucleus accumbens of the rat,” J. Neurochem., No. 70, 384–390 (1998).Google Scholar
  27. 27.
    A. J. Fulford and C. A. Marsden, “Effect of isolation-rearing on noradrenaline release in rat hypothalamus and hippocampus in vitro,” Brain Res., No. 748, 93–99 (1997).Google Scholar
  28. 28.
    A. J. Fulford and C. A. Marsden, “Social isolation in the rat enhances α2-autoreceptor function in the hippocampus in vivo,” Neuroscience, No. 77, 57–64 (1997).Google Scholar
  29. 29.
    C. Gentsch, M. Lichtsteiner, and H. Feer, “Locomotor activity, defecation score and corticosterone levels during open-field exposure: a comparison among individually and group-housed rats and genetically selected rat lines,” Physiol. Behav., No. 27, 183–186 (1981).Google Scholar
  30. 30.
    C. Gentsch, M. Lichtsteiner, K. Kraeuchi, and H. Feer, “Different reaction patterns in individually and socially reared rats during exposure to novel environments,” Behav. Brain Res., No. 4, 45–54 (1982).Google Scholar
  31. 31.
    M. A. Geyer, N. R. Swerdlow, R. S. Mansbach, and D. L. Braff, “Startle response models of sensorimotor gating and habituation deficits in schizophrenia,” Brain Res. Byull., No. 25, 485–498 (1990).Google Scholar
  32. 32.
    M. A. Geyer, L. S. Wilkinson, T. Humby, and T. W. Robbins, “Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia,” Biol. Psychiatry, No. 34, 361–372 (1993).Google Scholar
  33. 33.
    A. Globus, M. R. Rosenzweig, E. L. Bennett, and M. Diamond, “Effects of differential experience on dendritic spine counts in rat cerebral cortex,” J. Comp. Physiol. Psychol., No. 82, 175–181 (1973).Google Scholar
  34. 34.
    C. Grillon, R. Ameli, D. S. Charney, J. Krystal, and D. L. Braff, “Startle gating deficits occur across prepulse intensities in schizophrenic patients,” Biol. Psychiatry, No. 32, 939–943 (1992).Google Scholar
  35. 35.
    F. S. Hall, T. Humby, L. S. Wilkinson, and T. W. Robbins, “The effects of isolation-rearing of rats on behavioral responses to food and environmental novelty,” Physiol. Behav., No. 62, 281–290 (1997).Google Scholar
  36. 36.
    F. S. Hall, L. S. Wilkinson, T. Humby, W. Inglis, D. A. Kendall, C. A. Marsden, and T. W. Robbins, “Isolation rearing in rats: pre-and postsynaptic changes in striatal dopaminergic systems,” Pharmacol. Biochem. Behav., No. 59, 859–872 (1998).Google Scholar
  37. 37.
    C. J. Harmer and G. D. Phillips, “Isolation rearing enhances acquisition in a conditioned inhibition paradigm,” Physiol Behav., No. 65, 525–533 (1998).Google Scholar
  38. 38.
    C. J. Harmer and G. D. Phillips, “Isolation rearing enhances the rate of acquisition of a discriminative approach task but does not affect the efficacy of conditioned reward,” Physiol. Behav., No. 63, 177–184 (1998).Google Scholar
  39. 39.
    A. Hatch, G. S. Wiberg, T. Balazs, and H. C. Grice, “Long-term isolation stress in rats,” Science, No. 208, 507 (1963).Google Scholar
  40. 40.
    D. O. Hebb, “The effects of early experience on problem solving at maturity,” Am. Psychol., No. 2, 306–307 (1947).Google Scholar
  41. 41.
    P. K. Hitchcott, C. M. T. Bonardi, and G. D. Phillips, “Enhanced stimulus-reward learning by intra-amygdala administration of D3 dopamine receptor agonist,” Psychopharmacology (Berlin), No. 133, 240–248 (1997).Google Scholar
  42. 42.
    P. K. Hitchott, C. J. Harmer, and G. D. Phillips, “Enhanced acquisition of discriminative approach following intra-amygdala amphetamine,” Psychopharmacology (Berlin), No. 132, 237–246 (1997).Google Scholar
  43. 43.
    R. R. Holson, “Feeding neophobia: A possible explanation for the differential maze performance of rats reared in enriched or isolated environments,” Physiol. Behav., No. 38, 191–201 (1986).Google Scholar
  44. 44.
    R. R. Holson, A. C. Scallet, S. F. Ali, and B. B. Turner, “'Isolation stress' revisited: isolation rearing effects depend on animal care methods,” Physiol. Behav., No. 49, 1107–1118 (1991).Google Scholar
  45. 45.
    K. Hori, J. Tanaka, and M. Nomura, “Effects of discrimination learning on the rat amygdala release: a microdialysis study,” Brain Res., No. 621, 296–300 (1993).Google Scholar
  46. 46.
    M. Ichikawa, M. Matsuoka, and Y. Mori, “Effect of differential rearing on synapses and soma size in rat amygdaloid nucleus,” Synapse, No. 13, 50–56 (1993).Google Scholar
  47. 47.
    G. H. Jones, T. D. Hernandez, D. A. Kendall, C. A. Marsden, and T. W. Robbins, “Dopaminergic and serotonergic function following isolation rearing in rats. a study of behavioral responses and postmortem and in vivo neurochemistry,” Pharmacol. Biochem. Behav., No. 43, 17–35 (1992).Google Scholar
  48. 48.
    G. H. Jones, C. A. Marsden, and T. W. Robbins, “Increased sensitivity to amphetamine and reward-related stimuli following social isolation in rats: possible disruption of dopamine-dependent mechanisms of the nucleus accumbens,” Psychopharmacology, No. 102, 364–372 (1990).Google Scholar
  49. 49.
    G. H. Jones, C. A. Marsden, and T. W. Robbins, “Behavioral rigidity and rule-learning deficits following isolation-reaing in the rat: neurochemical correlates,” Behav. Brain Res., No. 43, 35–50 (1991).Google Scholar
  50. 50.
    G. H. Jones, T. W. Robbins, and C. A. Marsden, “Isolation-rearing retards the acquisition of schedule-induced polydipsia in rats,” Physiol. Behav., No. 45, 71–77 (1989).Google Scholar
  51. 51.
    J. N. Joyce, “The dopamine hypothesis of schizophrenia: limbic interaction with serotonin and norepinephrine,” Psychopharmacology, No. 112, S16–S34 (1993).Google Scholar
  52. 52.
    J. M. Juraska, C. Henderson, and J. Muller, “Differential rearing experience, gender and radial maze performance,” Dev. Psychobiol., No. 17, 209–215 (1984).Google Scholar
  53. 53.
    M. S. Kaplan and D. H. Bell, “Neuronal proliferation in the 9-month-old rodent - radioautographic study of granule cells in the hippocampus,” Exp. Brain Res., No. 52, 1–5 (1983).Google Scholar
  54. 54.
    M. S. Kaplan and D. H. Bell, “Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus,” J. Neurosci., No. 4, 1429–1441 (1984).Google Scholar
  55. 55.
    M. S. Kaplan and J. W. Hinds, “Neurogenesis in the adult rat: electron microscopic analysis of the light radioautographs,” Science, No. 197, 1092–1094 (1977).Google Scholar
  56. 56.
    N. Karki, R. Kuntzman, and B. B. Brodie, “Norepinephrine and serotonin brain levels at various stages of ontogenic development,” Fed. Proc., No. 19, 282 (1960).Google Scholar
  57. 57.
    K. Konrad and R. Melzack, “Novelty-enhancement effects associated with early sensorisocial isolation,” Psychol. Byull., No. 82, 986–995 (1975).Google Scholar
  58. 58.
    G. W. Kraemer, M. H. Ebert, C. R. Lake, and W. T. McKinney, “Hypersensitivity to d-amphetamine several years after early social deprivation in rhesus monkeys,” Psychopharmacology, No. 82, 266–271 (1984).Google Scholar
  59. 59.
    G. W. Kraemer and W. T. McKinney, “Social separation increases alcohol consumption in rhesus monkeys,” Psychopharmacology, No. 86, 182–189 (1985).Google Scholar
  60. 60.
    D. Krech, M. R. Rosenzweig, and E. L. Bennett, “Relations between brain chemistry and problem-solving among rats raised in enriched and impoverished environments,” J. Comp. Physiol. Psychol., No. 55, 801–807 (1962).Google Scholar
  61. 61.
    L. P. Lanier and R. L. Issacson, “Early developmental changes in the locomotor response to amphetamine and their relation to hippocampal function,” Brain Res., No. 126, 567–575 (1977).Google Scholar
  62. 62.
    M. D. S. Lapiz, Y. Mateo, T. L. Parker, and C. A. Marsden, “Central noradrenergic depletion enhanced hole-poking behavior in isolated rats,” Soc. Neurosci. Abstr., No. 25(2), 1876 (1999).Google Scholar
  63. 63.
    M. D. S. Lapiz, Y. Mateo, S. Durkin, S. Muchimapura, T. L. Parker, and C. A. Marsden, “Central noradrenergic depletion in isolated rats enhances retention but not acquisition in the water maze,” Behav. Pharmacol (Suppl.), No. 10, S55 (1999).Google Scholar
  64. 64.
    M. D. S. Lapiz, Y. Mateo, and C. A. Marsden, “Effects of noradrenaline depletion in the brain on response to novelty in isolation reared rats,” Psychopharmacology (submitted) (2000).Google Scholar
  65. 65.
    M. D. S. Lapiz, Y. Mateo, T. L. Parker, and C. A. Marsden, “Noradrenergic involvement in the exploratory behavior of isolation reared rats,” Br. J. Pharmacol. (Suppl.), No. 63 (in press) (2000).Google Scholar
  66. 66.
    M. D. S. Lapiz, T. L. Parker, and C. A. Marsden, “Changes in phencyclidine-induced behavior following isolation rearing in the rat,” Br. J. Pharmacol. (Suppl.), No. 128, 201P (1999).Google Scholar
  67. 67.
    M. D. S. Lapiz, T. L. Parker, and C. A. Marsden, “Effects of acute and subchronic phencyclidine administration on the locomotor behavior of isolation-reared rats,” J. Psychopharmacol. (Suppl. A), No. 13, A12 (1999).Google Scholar
  68. 68.
    M. D. S. Lapiz, T. L. Parker, and C. A. Marsden, “Social isolation affects response to novelty and to d-amphetamine,” Proc. Aust. Neurosci. Soc., No. 10, 200 (1999).Google Scholar
  69. 69.
    L. J. Martin, D. M. Spicer, M. H. Lewis, J. P. Gluck, and L. C. Cork, “Social deprivation in infact rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions,” J Neurosci., No. 11, 3344–3358 (1991).Google Scholar
  70. 70.
    E. Masliah, R. D. Terry, M. Alford, and R. DeTeresa, “Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections,” J. Histochem. Cytochem., No. 38, 837–844 (1990).Google Scholar
  71. 71.
    W. A. Mason, R. K. Davenport, and E. W. Menzel, “Early experience and the social development of rhesus monkeys and chimpanzees,” in: Newton G., Levine S. (eds.), Early Experience and Behavior, Thomas, Springfield, Illinois (1968).Google Scholar
  72. 72.
    M. J. Morgan, “Effects of post-weaning environment on learning in the rat,” Anim. Behav., No. 21, 429–442 (1973).Google Scholar
  73. 73.
    M. Morgan and D. Einon, “Incentive motivation and behavioral inhibition in socially-isolated rats,” Physiol. Behav., No. 15, 405–409 (1975).Google Scholar
  74. 74.
    A. Morinan and V. Parker, “Are socially isolated rats anxious?” Br. J. Pharmacol., No. 86, 460 (1986).Google Scholar
  75. 75.
    J. H. Morrison, P. R. Hof, W. Janssen, J. L. Bassett, S. L. Foote, G. W. Kraemer, and W. T. McKinney, “Quantitative neuroanatomic analyses of cerebral cortex in rhesus monkey from different rearing conditions,” Proc. Soc. Neurosci., No. 16, 789, P12 (1990).Google Scholar
  76. 76.
    S. Muchimapura, R. Mason, and C. A. Marsden, “Effect of social isolation on hippocampal 5-HT1A receptor activity in the Lister Hooded rat,” Br. J. Pharmacol (Suppl.), No. 128, 203 (1999).Google Scholar
  77. 77.
    S. Muchimapura, R. Mason, and C. A. Marsden, “Effects of social isolation on hippocampal neuronal activity in vitro,” J. Psychopharmacology (Suppl.), No. 13 (1999).Google Scholar
  78. 78.
    J. C. Neill and B. Costall, “The effect of isolation rearing on ethanol and saccharin preference in the rat,” J. Psychopharmacology (Suppl.), No. 10(3), A10 (1996).Google Scholar
  79. 79.
    M. G. Packard, L. Cahill, and J. L. McGaugh, “Amydala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes,” Proc. Nat. Acad. Sci. USA, No. 91, 8477–8481 (1994).Google Scholar
  80. 80.
    G. D. Phillips, S. R. Howes, R. B. Whitelaw, L. S. Wilkinson, and T. W. Robbins, “Isolation rearing enhances the locomotor response to cocaine and a novel environment, but impairs the intravenous administration of cocaine,” Psychopharmacology, No. 115, 407–418 (1994)Google Scholar
  81. 81.
    G. P. Sackett, “Prospects for research on schizophrenia. 3. Neurophysiology. Isolation rearing in primates,” Neurosci. Res. Prog. Byull., No. 10, 388–390 (1972).Google Scholar
  82. 82.
    B. J. Sahakian and T. W. Robbins, “Isolation-rearing enhances tail pinch-induced oral behavior in rats,” Physiol. Behav., No. 18, 53–58 (1977).Google Scholar
  83. 83.
    B. J. Sahakian, T. W. Robbins, and S. D. Iversen, “The effects of isolation rearing on exploration in the rat,” Anim. Learn. Behav., No. 5, 193–198 (1977).Google Scholar
  84. 84.
    B. J. Sahakian, T. W. Robbins, M. J. Morgan, and S. D. Iversen, “The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats,” Brain Res., No. 84, 195–205 (1975).Google Scholar
  85. 85.
    P. F. D. Seitz, “Infantile experience and adult behavior in animal subjects. II. Age of separation from the mother and adult behavour in the cat,” Psychosom. Med., No. 21, 353–378 (1959).Google Scholar
  86. 86.
    B. V. J. Siegel, M. S. Buchsbaum, W. E. J. Bunney, L. A. Gottschalk, R. J. Haier, J. B. Lohr, S. Lottenberg, A. Najafi, K. H. Neuchterlein, S. G. Potkin, and J. C. Wu, “Cortico-striatal thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients,” Am. J. Psychiatry, No. 150, 1325–1336 (1993).Google Scholar
  87. 87.
    A. M. Sirevaag and W. T. Greenough, “Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, buotons, dendrites, and capillaries,” Brain Res., No. 424, 320–332 (1987).Google Scholar
  88. 88.
    J. K. Smith, J. C. Neill, and B. Costall, “Post-weaning housing conditions influence the behavioral effects of cocaine and d-amphetamine,” Psychopharmacology, No. 131, 23–33 (1997).Google Scholar
  89. 89.
    S. C. Stanford, V. Parker, and A. Morinan, “Deficits in exploratory behavior in socially-isolated rats are not accompanied by changes in cerebral cortical adrenoceptor binding,” J. Aff. Dis., No. 15, 175–180 (1988).Google Scholar
  90. 90.
    N. R. Swerdlow, S. B. Caine, D. L. Braff, and M. A. Geyer, “The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications,” J. Psychopharmacol., No. 6, 176–190 (1992).Google Scholar
  91. 91.
    L. A. Syme, “Social isolation at weaning, some effects on two measures of activity,” Anim. Learn. Behav., No. 1, 161–163 (1973).Google Scholar
  92. 92.
    N. B. Thoa, Y. Tizabi, and D. M. Jacobowitz, “The effect of prolonged isolation on the catecholamine and serotonin concentrations of discrete areas of the rat brain,” in: E. Usdin, R. Kvetnansky, and I. J. Kopin (eds.), Catecholamines and Stress, Pergamon Press, Oxford (1976) pp.61–66.Google Scholar
  93. 93.
    N. B. Thoa, Y. Tizabi, and D. M. Jacobowitz, “The effects of isolation on catecholamine concentration and turnover in discrete areas of the rat brain,” Brain Res., No. 131, 259–269 (1977).Google Scholar
  94. 94.
    L. Valzelli, “The isolation syndrome in mice,” Psychopharmacology, No. 31, 305–320 (1973).Google Scholar
  95. 95.
    G. B. Varty, C. A. Marsden, and G. A. Higgins, “Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats,” Brain Res., No. 824, 197–203 (1999).Google Scholar
  96. 96.
    F. R. Volkmar and W. T. Greenough, “Rearing complexity affects branching of dendrites in the visual cortical synapses of rats: preliminary results,” Behav. Biol., No. 7, 279–284 (1972).Google Scholar
  97. 97.
    I. C. Weiss, J. Feldon, and A. M. Domeney, “Isolation rearing-induced disruption of prepulse inhibition: Further evidence for fragility of the response,” Behav. Pharmacol., No. 10, 139–149 (1999).Google Scholar
  98. 98.
    L. S. Wilkinson, S. S. Killcross, T. Humby, F. S. Hall, M. A. Geyer, and T. W. Robbins, “Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition,” Neuropsychopharmacology, No. 10, 63–72 (1994).Google Scholar
  99. 99.
    B. E. Will, M. R. Rosenzweig, and E. L. Bennett, “Effects of differential environments on recovery from neonatal brain lesions, measured by problem-solving scores and brain dimensions,” Physiol. Behav., No. 16, 603–611 (1976).Google Scholar
  100. 100.
    P. Willner, “The validity of animal models of depression,” Psychopharmacology, No. 83, 1–16 (1984).Google Scholar
  101. 101.
    C. A. Wilmot, C. VanderWende, and M. T. Spoerlein, “Behavioral and biochemical studies of dopamine receptor sensitivity in differentially housed mice,” Psychopharmacology, No. 89, 364–369 (1986).Google Scholar
  102. 102.
    N. Wongwitdecha and C. A. Marsden, “Effect of social isolation on the reinforcing properties of morphine in the conditioned place preference test,” Pharmacol. Biochem. Behav., No. 53, 531–534 (1996).Google Scholar
  103. 103.
    N. Wongwitdecha and C. A. Marsden, “Effects of social isolation on learning in the Morris water maze,” Brain Res., No. 715, 119–124 (1996).Google Scholar
  104. 104.
    N. Wongwitdecha and C. A. Marsden, “Social isolation increases aggressive behavior and alters the effects of diazepam in the rat social interaction test,” Behav. Brain Res., No. 75, 27–32 (1996).Google Scholar
  105. 105.
    P. J. Woods, A. S. Fiske, and S. I. Ruckelshaus, “The effects of drives conflicting with exploration on the problem solving behavior of rats reared in free and restricted environments,” J. Comp. Physiol. Psychol., No. 54, 167–169 (1961).Google Scholar
  106. 106.
    I. K. Wright, H. Ismail, N. Upton, and C. A. Marsden, “Resocialization of isolation-reared rats do not alter their anxiogenic profile in the elevated X-maze model of anxiety,” Physiol. Behav., No. 50, 1129–1132 (1991).Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • M. D. S. Lapiz
    • 1
  • A. Fulford
    • 2
  • S. Muchimapura
    • 1
  • R. Mason
    • 1
  • T. Parker
    • 1
  • C. A. Marsden
    • 1
  1. 1.School of Biomedical SciencesUniversity of Nottingham Medical School, Queen's Medical CentreNottinghamUnited Kingdom
  2. 2.Department of Biological and Biomedical Sciences, Faculty of Applied ScienceUniversity of West EnglandBristolUnited Kingdom

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