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

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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.

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REFERENCES

  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. 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. 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. M. E. Bitterman, “The evolution of intelligence,” Scientific American, No. 212, 92–100 (1965).

    Google Scholar 

  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. 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. 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. 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. 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. J. T. Coyle and D. Henry, “Catecholamines in foetal and newborn rat brain,” J. Neurochem., No. 21, 61–67. 1973.

    Google Scholar 

  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. 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. 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. 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).

  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. D. O. Hebb, “The effects of early experience on problem solving at maturity,” Am. Psychol., No. 2, 306–307 (1947).

    Google Scholar 

  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. J. N. Joyce, “The dopamine hypothesis of schizophrenia: limbic interaction with serotonin and norepinephrine,” Psychopharmacology, No. 112, S16–S34 (1993).

    Google Scholar 

  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. 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. 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. 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. 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. K. Konrad and R. Melzack, “Novelty-enhancement effects associated with early sensorisocial isolation,” Psychol. Byull., No. 82, 986–995 (1975).

    Google Scholar 

  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. G. W. Kraemer and W. T. McKinney, “Social separation increases alcohol consumption in rhesus monkeys,” Psychopharmacology, No. 86, 182–189 (1985).

    Google Scholar 

  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. 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. 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. 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. 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).

  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).

  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).

  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. 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. 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. 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. 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. M. J. Morgan, “Effects of post-weaning environment on learning in the rat,” Anim. Behav., No. 21, 429–442 (1973).

    Google Scholar 

  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. A. Morinan and V. Parker, “Are socially isolated rats anxious?” Br. J. Pharmacol., No. 86, 460 (1986).

    Google Scholar 

  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. 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. S. Muchimapura, R. Mason, and C. A. Marsden, “Effects of social isolation on hippocampal neuronal activity in vitro,” J. Psychopharmacology (Suppl.), No. 13 (1999).

  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. L. Valzelli, “The isolation syndrome in mice,” Psychopharmacology, No. 31, 305–320 (1973).

    Google Scholar 

  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. 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. 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. 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. 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. P. Willner, “The validity of animal models of depression,” Psychopharmacology, No. 83, 1–16 (1984).

    Google Scholar 

  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. 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. 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. 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. 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. 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 

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Lapiz, M.D.S., Fulford, A., Muchimapura, S. et al. Influence of Postweaning Social Isolation in the Rat on Brain Development, Conditioned Behavior, and Neurotransmission. Neurosci Behav Physiol 33, 13–29 (2003). https://doi.org/10.1023/A:1021171129766

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