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Animal Models of Self-Injurious Behavior: An Update

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Psychiatric Disorders

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2011))

Abstract

Although self-injurious behavior is a common comorbid behavior problem among individuals with neurodevelopmental disorders, little is known about its etiology and underlying neurobiology. Interestingly, it shows up in various forms across patient groups with distinct genetic errors and diagnostic categories. This suggests that there may be shared neuropathology that confers vulnerability in these disparate groups. Convergent evidence from clinical pharmacotherapy, brain imaging studies, postmortem neurochemical analyses, and animal models indicates that dopaminergic insufficiency is a key contributing factor. This chapter provides an overview of studies in which animal models have been used to investigate the biochemical basis of self-injury and highlights the convergence in findings between these models and expression of self-injury in humans.

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References

  1. Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36:561–570

    CAS  PubMed  Google Scholar 

  2. Nyhan WL (1968) Seminars on the Lesch-Nyhan syndrome: summary of clinical features. Fed Proc 27:1034–1041

    CAS  PubMed  Google Scholar 

  3. Stein DJ, Keating J, Zar HJ, Hollander E (1994) A survey of the phenomenology and pharmacotherapy of compulsive and impulsive-aggressive symptoms in Prader-Willi syndrome. J Neuropsychiatry Clin Neurosci 6:23–29

    CAS  PubMed  Google Scholar 

  4. Symons FJ, Butler MG, Sanders MD, Feurer ID, Thompson T (1999) Self-injurious behavior and Prader-Willi syndrome: behavioral forms and body locations. Am J Ment Retard 104:260–269

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hardiman RL, McGill P (2018) How common are challenging behaviours amongst individuals with Fragile X syndrome? A systematic review. Res Dev Disabil 76:99–109

    PubMed  Google Scholar 

  6. Hall SS, Hustyi KM, Barnett RP (2018) Examining the influence of social-environmental variables on self-injurious behaviour in adolescent boys with fragile X syndrome. J Intellect Disabil Res 62(12):1072–1085

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Poustka F, Lisch S (1993) Autistic behaviour domains and their relation to self-injurious behaviour. Acta Paedopsychiatr 56:69–73

    CAS  PubMed  Google Scholar 

  8. Wing L (1975) The syndrome of early childhood autism. Br J Psychiatry Spec No 9:349–360

    CAS  PubMed  Google Scholar 

  9. Oliver C, Murphy GH, Corbett JA (1987) Self-injurious behavior in people with mental handicap: a total population study. J Ment Defic Res 31:147–162

    PubMed  Google Scholar 

  10. Ando H, Yoshimura I (1979) Speech skill levels and prevalence of maladaptive behaviors in autistic and mentally retarded children: a statistical study. Child Psychiatry Hum Dev 10:85–90

    CAS  PubMed  Google Scholar 

  11. Schroeder SR, Schroeder CS, Smith B, Dalldorf J (1978) Prevalence of self-injurious behaviors in a large state facility for the retarded: a three-year follow-up study. J Autism Child Schizophr 8:261–269

    CAS  PubMed  Google Scholar 

  12. Anderson LT, Ernst M (1994) Self-injury in Lesch-Nyhan disease. J Autism Dev Disord 24:67–81

    CAS  PubMed  Google Scholar 

  13. Clarke DJ, Waters J, Corbett JA (1989) Adults with Prader-Willi syndrome: abnormalities of sleep and behaviour. J R Soc Med 82:21–24

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Baghdadli A, Pascal C, Grisi S, Aussilloux C (2003) Risk factors for self-injurious behaviours among 222 young children with autistic disorders. J Intellect Disabil Res 47:622–627

    CAS  PubMed  Google Scholar 

  15. Sigafoos J, Elkins J, Kerr M, Attwood T (1994) A survey of aggressive behaviour among a population of persons with intellectual disability in Queensland. J Intellect Disabil Res 38:369–381

    PubMed  Google Scholar 

  16. Durand VM, Carr EG (1985) Self-injurious behavior: motivating conditions and guidelines for treatment. School Psychol Rev 14:171–176

    Google Scholar 

  17. Carr EG, Durand VM (1985) Reducing behavior problems through functional communication training. J Appl Behav Anal 18:111–126

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Iwata BA, Dorsey MF, Slifer KJ, Bauman KE, Richman GS (1982) Toward a functional analysis of self-injury, analysis & intervention. Dev Dis 2:3–30

    Google Scholar 

  19. Bird F, Dores PA, Moniz D, Robinson J (1989) Reducing severe aggressive and self-injurious behaviors with functional communication training. Am J Ment Retard 94:37–48

    CAS  PubMed  Google Scholar 

  20. Sigafoos J, Meikle B (1996) Functional communication training for the treatment of multiply determined challenging behavior in two boys with autism. Behav Modif 20:60–84

    CAS  PubMed  Google Scholar 

  21. Barron JL, Sandman CA (1984) Self-injurious behavior and stereotypy in an institutionalized mentally retarded population. Appl Res Ment Retard 5:499–511

    CAS  PubMed  Google Scholar 

  22. Griffin JC, Williams DE, Stark MT, Altmeyer BK, Mason M (1986) Self-injurious behavior: a state-wide prevalence survey of the extent and circumstances. Appl Res Ment Retard 7:105–116

    CAS  PubMed  Google Scholar 

  23. Maurice P, Trudel G (1982) Self-injurious behavior prevalence and relationships to environmental events. Monogr Am Assoc Ment Defic 5:81–103

    Google Scholar 

  24. Singh NN (1977) Prevalence of self-injury in institutionalised retarded children. N Z Med J 86:325–327

    CAS  PubMed  Google Scholar 

  25. Favell JE, McGimsey JF, Schell RM (1982) Treatment of self-injury by providing alternate sensory activities, analysis & intervention. Dev Dis 2:83–104

    Google Scholar 

  26. Favell JE, Azrin NA, Baumeister AA, Carr EG, Dorsey MF, Forehand R, Foxx RM, Lovaas OI, Rincover A, Risley T, Romanczyk RG, Russo DC, Schroeder SR, Solnick JV (1982) The treatment of self-injurious behavior. Behav Ther 13:529–554

    Google Scholar 

  27. Beckett C, Bredenkamp D, Castle J, Groothues C, O’Connor TG, Rutter M (2002) Behavior patterns associated with institutional deprivation: a study of children adopted from Romania. J Dev Behav Pediatr 23:297–303

    Google Scholar 

  28. Sovner R, Fogelman S (1996) Irritability and mental retardation. Semin Clin Neuropsychiatry 1:105–114

    CAS  PubMed  Google Scholar 

  29. Lindauer SE, DeLeon IG, Fisher WW (1999) Decreasing signs of negative affect and correlated self-injury in an individual with mental retardation and mood disturbances. J Appl Behav Anal 32:103–106

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Verhoeven WMA, Tuinier S, van den Berg YWMM, Coppus AMW, Fekkes D, Pepplinkhuizen L, Thijssen JHH (1999) Stress and self-injurious behavior; hormonal and serotonergic parameters in mentally retarded subjects. Pharmacopsychiatry 32:13–20

    CAS  PubMed  Google Scholar 

  31. Rojahn J, Esbensen AJ (2002) Epidemiology of self-injurious behavior in mental retardation: a review. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene-brain-behavior relationships. American Psychological Association, Washington, DC, pp 41–77

    Google Scholar 

  32. Durand VM, Carr EG (1991) Functional communication training to reduce challenging behavior: maintenance and application in new settings. J Appl Behav Anal 24:251–264

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Azrin NH, Gottlieb L, Hughart L, Wesolowski MD, Rahn T (1975) Eliminating self-injurious behavior by educative procedures. Behav Res Ther 13:101–111

    CAS  PubMed  Google Scholar 

  34. Cowdery GE, Iwata BA, Pace GM (1990) Effects and side effects of DRO as treatment for self-injurious behavior. J Appl Behav Anal 23:497–506

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Tarpley HD, Schroeder SR (1979) Comparison of DRO and DRI on rate of suppression of self-injurious behavior. Am J Ment Defic 84:188–194

    CAS  PubMed  Google Scholar 

  36. Bruhl HH, Fielding L, Joyce M, Peters W, Wieseler N (1982) Thirty-month demonstration project for treatment of self-injurious behavior in severely retarded individuals. Monogr Am Assoc Ment Defic 5:191–275

    Google Scholar 

  37. Vollmer TR (1994) The concept of automatic reinforcement: implications for behavioral research in developmental disabilities. Res Dev Disabil 15:187–207

    CAS  PubMed  Google Scholar 

  38. Iwata BA, Pace GM, Dorsey MF, Zarcone JR, Vollmer TR, Smith RG, Rodgers TA, Lerman DC, Shore BA, Mazalesk JL et al (1994) The functions of self-injurious behavior: an experimental-epidemiological analysis. J Appl Behav Anal 27:215–240

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Underwood LA, Figueroa RG, Thyer BA, Nzeocha A (1989) Interruption and DRI in the treatment of self-injurious behavior among mentally retarded and autistic self-restrainers. Behav Modif 13:471–481

    CAS  PubMed  Google Scholar 

  40. Olson L, Houlihan D (2000) A review of behavioral treatments used for Lesch-Nyhan syndrome. Behav Modif 24:202–222

    CAS  PubMed  Google Scholar 

  41. Newcomb ET, Hagopian LP (2018) Treatment of severe problem behaviour in children with autism spectrum disorder and intellectual disabilities. Int Rev Psychiatry 30:96–109

    PubMed  Google Scholar 

  42. Seegmiller JE, Rosenbloom FM, Kelley WN (1967) Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155:1682–1684

    CAS  PubMed  Google Scholar 

  43. Lloyd KG, Hornykiewicz O, Davidson L, Shannak K, Farley I, Goldstein M, Shibuya M, Kelley WN, Fox IH (1981) Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. N Engl J Med 305:1106–1111

    CAS  PubMed  Google Scholar 

  44. Ernst M, Zametkin AJ, Matochik JA, Pascualvaca D, Jons PH, Hardy K, Hankerson JG, Doudet DJ, Cohen RM (1996) Presynaptic dopaminergic deficits in Lesch-Nyhan disease. N Engl J Med 334:1568–1572

    CAS  PubMed  Google Scholar 

  45. Ernst M, Zametkin AJ, Matochik JA, Pascualvaca D, Cohen RM (1997) Low medial prefrontal dopaminergic activity in autistic children. Lancet 350:638

    CAS  PubMed  Google Scholar 

  46. Brucke T, Sofic E, Killian W, Rett A, Riederer P (1987) Reduced concentrations and increased metabolism of biogenic amines in a single case of Rett-syndrome: a postmortem brain study. J Neural Transm 68:315–324

    CAS  PubMed  Google Scholar 

  47. Saito Y, Ito M, Hanaoka S, Ohama E, Akaboshi S, Takashima S (1999) Dopamine receptor upregulation in Lesch-Nyhan syndrome: a postmortem study. Neuropediatrics 30:66–71

    CAS  PubMed  Google Scholar 

  48. Rosenberger-Debiesse J, Coleman M (1986) Preliminary evidence for multiple etiologies in autism. J Autism Dev Disord 16:385–392

    CAS  PubMed  Google Scholar 

  49. Page T, Coleman M (1998) De novo purine synthesis is increased in the fibroblasts of purine autism patients. Adv Exp Med Biol 431:793–796

    CAS  PubMed  Google Scholar 

  50. Sweetman L, Nyhan WL (1970) Detailed comparison of the urinary excretion of purines in a patient with the Lesch-Nyhan syndrome and a control subject. Biochem Med 4:121–134

    CAS  PubMed  Google Scholar 

  51. Sandman CA, Barron JL, Chicz-DeMet A, DeMet EM (1990) Plasma β-endorphin levels in patients with self-injurious behavior and stereotypy. Am J Ment Retard 95:84–92

    CAS  PubMed  Google Scholar 

  52. Coid J, Allolio B, Rees LH (1983) Raised plasma metenkephalin in patients who habitually mutilate themselves. Lancet 2:545–546

    CAS  PubMed  Google Scholar 

  53. Gillberg C, Terenius L, Lonnerholm G (1985) Endorphin activity in childhood psychosis. Spinal fluid levels in 24 cases. Arch Gen Psychiatry 42:780–783

    CAS  PubMed  Google Scholar 

  54. Sandman CA (1988) β-endorphin disregulation in autistic and self-injurious behavior: a neurodevelopmental hypothesis. Synapse 2:193–199

    CAS  PubMed  Google Scholar 

  55. Willemsen-Swinkels SHN, Buitelaar JK, Weijnen FG, Thijssen JHH, Van Engeland H (1996) Plasma beta-endorphin concentrations in people with learning disability and self-injurious and/or autistic behaviour. Br J Psychiatry 168:105–109

    CAS  PubMed  Google Scholar 

  56. Sandman CA, Hetrick W, Talyor D, Marion S, Chicz-DeMet A (2000) Uncoupling of proopiomelanocortin (POMC) fragments is related to self-injury. Peptides 21:785–791

    CAS  PubMed  Google Scholar 

  57. Jankovic J, Caskey TC, Stout JT, Butler IJ (1988) Lesch-Nyhan syndrome: a study of motor behavior and cerebrospinal fluid neurotransmitters. Ann Neurol 23:466–469

    CAS  PubMed  Google Scholar 

  58. Symons FJ, Sutton KA, Walker C, Bodfish JW (2003) Altered diurnal pattern of salivary substance P in adults with developmental disabilities and chronic self-injury. Am J Ment Retard 108:13–18

    PubMed  Google Scholar 

  59. Kemp AS, Fillmore PT, Lenjavi MR, Lyon M, Chicz-DeMet A, Touchette PE, Sandman CA (2008) Temporal patterns of self-injurious behavior correlate with stress hormone levels in the developmentally disabled. Psychiatry Res 157:181–189

    CAS  PubMed  Google Scholar 

  60. Crews WDJ, Bonaventura S, Rowe FB, Bonsie D (1993) Cessation of long-term naltrexone therapy and self-injury: a case study. Res Dev Disabil 14:331–340

    PubMed  Google Scholar 

  61. Gillman MA, Sandyk R (1985) Opiatergic and dopaminergic function in Lesch-Nyhan syndrome. Am J Psychiatry 142:1226

    CAS  PubMed  Google Scholar 

  62. Herman BH, Hammock MK, Arthur-Smith A, Egan J, Chatoor I, Werner A, Zelnick N (1987) Naltrexone decreases self-injurious behavior. Ann Neurol 22:550552

    Google Scholar 

  63. Richardson JS, Zaleski WA (1983) Naloxone and self-mutilation. Biol Psychiatry 18:99–101

    CAS  PubMed  Google Scholar 

  64. Sandman CA, Barron JL, Crinella FM, Donnelly JF (1987) Influence of naloxone on brain and behavior of a self-injurious woman. Biol Psychiatry 22:899–906

    CAS  PubMed  Google Scholar 

  65. Sandman CA, Barron JL, Colman H (1990) An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior. Am J Ment Retard 95:93102

    Google Scholar 

  66. Sandyk R (1985) Naloxone abolishes self-injuring in a mentally retarded child. Ann Neurol 17:520

    CAS  PubMed  Google Scholar 

  67. Benjamin E, Buot-Smith T (1993) Naltrexone and fluoxetine in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 32:870–873

    CAS  PubMed  Google Scholar 

  68. Symons FJ, Thompson A, Rodriguez MC (2004) Self-injurious behavior and the efficacy of naltrexone treatment: a quantitative synthesis. Ment Retard Dev Disabil Res Rev 10:193–200

    PubMed  Google Scholar 

  69. Willemsen-Swinkels SHN, Buitelaar JK, Nijhof GJ, Van Engeland H (1995) Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults - double-blind placebo-controlled studies. Arch Gen Psychiatry 52:766–773

    CAS  PubMed  Google Scholar 

  70. Davidson PW, Kleene BM, Carroll M, Rockowitz RJ (1983) Effects of naloxone on self-injurious behavior: a case study. Appl Res Ment Retard 4:1–4

    CAS  PubMed  Google Scholar 

  71. Allen SM, Rice SN (1996) Risperidone antagonism of self-mutilation in a Lesch-Nyhan patient. Prog Neuropsychopharmacol Biol Psychiatry 20:793–800

    CAS  PubMed  Google Scholar 

  72. Cohen SA, Ihrig K, Lott RS, Kerrick JM (1998) Risperidone for aggression and self-injurious behavior in adults with mental retardation. J Autism Dev Disord 28:229–233

    CAS  PubMed  Google Scholar 

  73. Horrigan JP, Barnhill LJ (1997) Risperidone and explosive aggressive autism. J Autism Dev Disord 27:313–323

    CAS  PubMed  Google Scholar 

  74. Gualtieri CT, Schroeder SR (1989) Pharmacotherapy for self-injurious behavior: preliminary tests of the D1 hypothesis. Psychopharmacol Bull 25:364–371

    CAS  PubMed  Google Scholar 

  75. Singh NN, Winton AS (1984) Behavioral monitoring of pharmacological interventions for self-injury. Appl Res Ment Retard 5:161–170

    CAS  PubMed  Google Scholar 

  76. Gedye A (1990) Dietary increase in serotonin reduces self-injurious behaviour in a Down’s syndrome adult. J Ment Defic Res 34:195–204

    PubMed  Google Scholar 

  77. Markowitz PI (1992) Effect of fluoxetine on self-injurious behavior in the developmentally disabled: a preliminary study. J Clin Psychopharmacol 12:27–31

    CAS  PubMed  Google Scholar 

  78. Sovner R, Fox CJ, Lowry MJ, Lowry MA (1993) Fluoxetine treatment of depression and associated self-injury in two adults with mental retardation. J Intellect Disabil Res 37:301–311

    PubMed  Google Scholar 

  79. Warnock JK, Kestenbaum T (1992) Pharmacologic treatment of severe skin-picking behaviors in Prader-Willi syndrome. Two case reports. Arch Dermatol 128:1623–1625

    CAS  PubMed  Google Scholar 

  80. Frith CD, Johnstone EC, Joseph MH, Powell RJ, Watts RWE (1976) Double-blind clinical trial of 5-hydroxytryptophan in a case of Lesch-Nyhan syndrome. J Neurol Neurosurg Psychiatry 39:656–662

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Ciaranello RD, Anders TF, Barchas JD, Berger PA, Cann HM (1976) The use of 5-hydroxytryptophan in a child with Lesch-Nyhan syndrome. Child Psychiatry Hum Dev 7:127–133

    CAS  PubMed  Google Scholar 

  82. Davanzo PA, Belin TR, Widawski MH, King BH (1998) Paroxetine treatment of aggression and self-injury in persons with mental retardation. Am J Ment Retard 102:427–437

    CAS  PubMed  Google Scholar 

  83. Anders TF, Cann HM, Ciaranello RD, Barchas JD, Berger PA (1978) Further observations on the use of 5-hydroxytryptophan in a child with Lesch-Nyhan syndrome. Neuropadiatrie 9:157–166

    CAS  PubMed  Google Scholar 

  84. Janowsky DS, Kraus JE, Barnhill J, Elamir B, Davis JM (2003) Effects of topiramate on aggressive, self-injurious, and disruptive/destructive behaviors in the intellectually disabled: an open-label retrospective study. J Clin Psychopharmacol 23:500–504

    CAS  PubMed  Google Scholar 

  85. Smathers SA, Wilson JG, Nigro MA (2003) Topiramate effectiveness in Prader-Willi syndrome. Pediatr Neurol 28:130–133

    Google Scholar 

  86. Shapira NA, Lessig MC, Murphy TK, Driscoll DJ, Goodman WK (2002) Topiramate attenuates self-injurious behaviour in Prader-Willi syndrome. Int J Neuropsychopharmacol 5:141–145

    CAS  PubMed  Google Scholar 

  87. Harlow HF, Harlow MK (1962) Social deprivation in monkeys. Scient Am 207:136–146

    CAS  Google Scholar 

  88. Novak MA, Crockett CM, Sackett GP (2002) Self-injurious behavior in captive macaque monkeys. In: Schroeder SR, Oster-Granite ML, Thompson T (eds) Self-injurious behavior: gene-brain-behavior relationships. American Psychological Association, Washington, DC, pp 151–161

    Google Scholar 

  89. Dodman NH, Normile JA, Shuster L, Rand W (1994) Equine self-mutilation syndrome (57 cases). J Am Vet Med Assoc 204:1219–1223

    CAS  PubMed  Google Scholar 

  90. McDonnell SM (2008) Practical review of self-mutilation in horses. Anim Reprod Sci 107:219–228

    PubMed  Google Scholar 

  91. Jenkins JR (2001) Feather picking and self-mutilation in psittacine birds. Vet Clin North Am Exot Anim Pract 4:651–667

    CAS  PubMed  Google Scholar 

  92. Schwartz S (1996) Animal behavior case of the month. A cat was referred for evaluation of self-mutilation. J Am Vet Med Assoc 208:1813–1814

    CAS  PubMed  Google Scholar 

  93. Schwartz S (2002) Separation anxiety syndrome in cats: 136 cases (1991–2000). J Am Vet Med Assoc 220:1028–1033

    PubMed  Google Scholar 

  94. Iglauer F, Beig C, Dimigen J, Gerold S, Gocht A, Seeburg A, Steier S, Willmann F (1995) Hereditary compulsive self-mutillating behaviour in laboratory rabbits. Lab Anim 29:385–393

    CAS  PubMed  Google Scholar 

  95. Goodall J (1986) The chimpanzees of Gombe: patterns of behavior. Belknap Press of Harvard University Press, Cambridge, MA

    Google Scholar 

  96. Breese GR, Baumeister AA, McCown TJ, Emerick SG, Frye GD, Crotty K, Mueller RA (1984) Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine. J Pharmacol Exp Ther 231:343–354

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Breese GR, Baumeister AA, McCown TJ, Emerick SG, Frye GD, Mueller RA (1984) Neonatal-6-hydroxydopamine treatment: model of susceptibility for self-mutilation in the Lesch-Nyhan syndrome. Pharmacol Biochem Behav 21:459–461

    CAS  PubMed  Google Scholar 

  98. Sivam SP, Pugazhenthi S, Pugazhenthi V, Brown H (2008) L-DOPA-induced activation of striatal p38MAPK and CREB in neonatal dopaminergic denervated rat: relevance to self-injurious behavior. J Neurosci Res 86:339–349

    CAS  PubMed  Google Scholar 

  99. Sivam SP (1989) D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior. Brain Res 500:119–130

    CAS  PubMed  Google Scholar 

  100. Neal BS, Joyce JN (1992) Neonatal 6-OHDA lesions differentially affect striatal D1 and D2 receptors. Synapse 11:35–46

    CAS  PubMed  Google Scholar 

  101. Molina-Holgado E, Van Gelder NM, Dewar KM, Reader TA (1995) Dopamine receptor alterations correlate with increased GABA levels in adult rat neostriatum: effects of a neonatal 6-hydroxydopamine denervation. Neurochem Int 27:443–451

    CAS  PubMed  Google Scholar 

  102. Radja F, El Mansari M, Soghomonian J-J, Dewar KM, Ferron A, Reader TA, Descarries L (1993) Changes of D1 and D2 receptors in adult rat neostriatum after neonatal dopamine denervation: in situ hybridization and iontophoresis. Neuroscience 57:635–648

    CAS  PubMed  Google Scholar 

  103. Breese GR, Baumeister AA, Napier TC, Frye GD, Mueller RA (1985) Evidence that D-1 dopamine receptors contribute to the supersensitive behavioral responses induced by l-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine. J Pharmacol Exp Ther 235:287–295

    CAS  PubMed  Google Scholar 

  104. Criswell HE, Mueller RA, Breese GR (1992) Pharmacologic evaluation of SCH-39166, A-69024, NO-0756, and SCH-23390 in neonatal-6-OHDA-lesioned rats. Further evidence that self-mutilatory behavior induced by L-DOPA is related to D1 dopamine receptors. Neuropsychopharmacology 7:95–103

    CAS  PubMed  Google Scholar 

  105. Criswell HE, Mueller RA, Breese GR (1988) Assessment of purine-dopamine interactions in 6-hydroxydopamine-lesioned rats: evidence for pre- and postsynaptic influences by adenosine. J Pharmacol Exp Ther 244:493–500

    CAS  PubMed  Google Scholar 

  106. Fletcher GH, Starr MS (1987) Topography of dopamine behaviours mediated by D1 and D2 receptors revealed by intrastriatal injection of SKF 38393, lisuride and apomorphine in rats with a unilateral 6-hydroxydopamine-induced lesion. Neuroscience 20:589–597

    CAS  PubMed  Google Scholar 

  107. Allen SM, Freeman JN, Davis WM (1998) Evaluation of risperidone in the neonatal 6-hydroxydopamine model of Lesch-Nyhan syndrome. Pharmacol Biochem Behav 59:327–330

    CAS  PubMed  Google Scholar 

  108. El Mansari M, Radja F, Ferron A, Reader TA, Molina-Holgado E, Descarries L (1994) Hypersensitivity to serotonin and its agonists in serotonin-hyperinnervated neostriatum after neonatal dopamine denervation. Eur J Pharmacol 261:171–178

    PubMed  Google Scholar 

  109. Jackson D, Abercrombie ED (1992) In vivo neurochemical evaluation of striatal serotonergic hyperinnervation in rats depleted of dopamine at infancy. J Neurochem 58:890–897

    CAS  PubMed  Google Scholar 

  110. Mrini A, Soucy J-P, Lafaille F, Lemoine P, Descarries L (1995) Quantification of the serotonin hyperinnervation in adult rat neostriatum after neonatal 6-hydroxydopamine lesion of nigral dopamine neurons. Brain Res 669:303–308

    CAS  PubMed  Google Scholar 

  111. Towle AC, Criswell HE, Maynard EH, Lauder JM, Joh TH, Mueller RA, Breese GR (1989) Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: an anatomical, biochemical and pharmacological study. Pharmacol Biochem Behav 34:367–374

    CAS  PubMed  Google Scholar 

  112. Allen SM, Davis WM (1999) Relationship of dopamine to serotonin in the neonatal 6-OHDA rat model of Lesch-Nyhan syndrome. Behav Pharmacol 10:467–474

    CAS  PubMed  Google Scholar 

  113. Stodgell CJ, Loupe PS, Schroeder SR, Tessel RE (1998) Cross-sensitization between footshock stress and apomorphine on self-injurious behavior and neostriatal catecholamines in a rat model of Lesch-Nyhan syndrome. Brain Res 783:10–18

    CAS  PubMed  Google Scholar 

  114. Sorg BA, Kalivas PW (1991) Effects of cocaine and footshock stress on extracellular dopamine levels in the ventral striatum. Brain Res 559:29–36

    CAS  PubMed  Google Scholar 

  115. Cross HA, Harlow HF (1965) Prolonged and progressive effects of partial isolation on the behavior of macaque monkeys. J Exp Res Pers 1:39–49

    Google Scholar 

  116. Gluck JP, Sackett GP (1974) Frustration and self-aggression in social isolate rhesus monkeys. J Abnorm Psychol 83:331–334

    CAS  PubMed  Google Scholar 

  117. Clarke AS, Ebert MH, Schmidt DE, McKinney WT, Kraemer GW (1999) Biogenic amine activity in response to fluoxetine and desipramine in differentially reared rhesus monkeys. Biol Psychiatry 46:221–228

    CAS  PubMed  Google Scholar 

  118. Lewis MH, Gluck JP, Beauchamp AJ, Keresztury MF, Mailman RB (1990) Long-term effects of early social isolation in Macaca mulatta: changes in dopamine receptor function following apomorphine challenge. Brain Res 513:67–73

    CAS  PubMed  Google Scholar 

  119. Martin LJ, Spicer DM, Lewis MH, Gluck JP, Cork LC (1991) Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions. J Neurosci 11:3344–3358

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Young LD, Suomi SS, Harlow HF, McKinney WT Jr (1973) Early stress and later response to separation in rhesus monkeys. Am J Psychiatry 130:400–405

    CAS  PubMed  Google Scholar 

  121. Davenport MD, Lutz CK, Tiefenbacher S, Novak MA, Meyer JS (2008) A rhesus monkey model of self-injury: effects of relocation stress on behavior and neuroendocrine function. Biol Psychiatry 63:990–996

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Tiefenbacher S, Novak MA, Jorgensen MJ, Meyer JS (2000) Physiological correlates of self-injurious behavior in captive, socially-reared rhesus monkeys. Psychoneuroendocrinology 25:799–817

    CAS  PubMed  Google Scholar 

  123. Tiefenbacher S, Novak MA, Marinus LM, Chase WK, Miller JA, Meyer JS (2004) Altered hypothalamic-pituitary-adrenocortical function in rhesus monkeys (Macaca mulatta) with self-injurious behavior. Psychoneuroendocrinology 29:501–515

    CAS  PubMed  Google Scholar 

  124. Fulford AJ, Marsden CA (1998) Effect of isolation-rearing on conditioned dopamine release in vivo in the nucleus accumbens of the rat. J Neurochem 70:384–390

    CAS  PubMed  Google Scholar 

  125. Peters JM (1967) Caffeine-induced hemorrhagic automutilation. Arch Int Pharmacodyn Ther 169:139–146

    CAS  Google Scholar 

  126. Hoefnagel D (1968) Seminars on the Lesch-Nyhan syndrome: summary. Fed Proc 27:1042–1046

    CAS  PubMed  Google Scholar 

  127. Ferrer I, Costell M, Grisolia S (1982) Lesch-Nyhan syndrome like behavior in rats from caffeine ingestion. FEBS Lett 141:275–278

    CAS  PubMed  Google Scholar 

  128. Minana MD, Portoles M, Jorda A, Grisolia S (1984) Lesch-Nyhan syndrome, caffeine model: increases of purine and pyrimidine enzymes in rat brain. J Neurochem 43:1556–1560

    CAS  PubMed  Google Scholar 

  129. Minana MD, Grisolia S (1986) Caffeine ingestion by rats increases noradrenaline turnover and results in self-biting. J Neurochem 47:728–732

    CAS  PubMed  Google Scholar 

  130. Mueller K, Saboda S, Palmour RA, Nyhan WL (1982) Self-injurious behaviour produced in rats by daily caffeine and continuous amphetamine. Pharmacol Biochem Behav 17:613–617

    CAS  PubMed  Google Scholar 

  131. Mueller K, Nyhan WL (1983) Clonidine potentiates drug induced self-injurious behavior in rats. Pharmacol Biochem Behav 18:891–894

    CAS  PubMed  Google Scholar 

  132. Kies SD, Devine DP (2004) Self-injurious behaviour: a comparison of caffeine and pemoline models in rats. Pharmacol Biochem Behav 79:587–598

    CAS  Google Scholar 

  133. Snyder SH (1985) Adenosine as a neuromodulator. In: Cowan WM, Shooter EM, Stevens CF, Thompson RF (eds) Annual review of neuroscience. Annual Reviews Inc., Palo Alto, CA, pp 103–124

    Google Scholar 

  134. Ferré S, Fuxe K, von Euler G, Johansson B, Fredholm BB (1992) Adenosine-dopamine interactions in the brain. Neuroscience 51:501–512

    PubMed  Google Scholar 

  135. Brown SJ, James S, Reddington M, Richardson PJ (1990) Both A1 and A2a purine receptors regulate striatal acetylcholine release. J Neurochem 55:31–38

    CAS  PubMed  Google Scholar 

  136. Brown SJ, Gill R, Evenden JL, Iversen SD, Richardson PJ (1991) Striatal A2 receptor regulates apomorphine-induced turning in rats with unilateral dopamine denervation. Psychopharmacology 103:78–82

    CAS  PubMed  Google Scholar 

  137. Casas-Bruge M, Almenar C, Grau IM, Jane J, Herrera-Marschitz M, Ungerstedt U (1985) Dopaminergic receptor supersensitivity in self-mutilatory behavior of Lesch-Nyhan disease. Lancet 1(8435):991–992

    CAS  PubMed  Google Scholar 

  138. King BH, Cromwell HC, Lee HT, Behrstock SP, Schmanke T, Maidment NT (1998) Dopaminergic and glutamatergic interactions in the expression of self-injurious behavior. Dev Neurosci 20:180–187

    CAS  Google Scholar 

  139. Everett GM (1976) Comparative pharmacology of amphetamine and pemoline on biogenic amine systems. Fed Proc 35:405

    Google Scholar 

  140. Cromwell HC, King BH, Levine MS (1997) Pemoline alters dopamine modulation of synaptic responses of neostriatal neurons in vitro. Dev Neurosci 19:497–504

    CAS  Google Scholar 

  141. King BH, Au D, Poland RE (1995) Pretreatment with MK-801 inhibits pemoline-induced self-biting behavior in prepubertal rats. Dev Neurosci 17:47–52

    CAS  Google Scholar 

  142. Mueller K, Hsiao S (1980) Pemoline-induced self-biting in rats and self-mutilation in the deLange syndrome. Pharmacol Biochem Behav 13:627–631

    CAS  PubMed  Google Scholar 

  143. Cromwell HC, Levine MS, King BH (1999) Cortical damage enhances pemoline-induced self-injurious behavior in prepubertal rats. Pharmacol Biochem Behav 62:223–227

    CAS  Google Scholar 

  144. Mueller K, Nyhan WL (1982) Pharmacologic control of pemoline induced self-injurious behavior in rats. Pharmacol Biochem Behav 16:957–963

    CAS  PubMed  Google Scholar 

  145. Genovese E, Napoli PA, Bolego-Zonta N (1969) Self-aggressiveness: a new type of behavioural change induced by pemoline. Life Sci 8:513–515

    CAS  Google Scholar 

  146. Mueller K, Hollingsworth E, Pettit H (1986) Repeated pemoline produces self-injurious behavior in adult and weanling rats. Pharmacol Biochem Behav 25:933938

    Google Scholar 

  147. Turner CA, Panksepp J, Bekkedal M, Borkowski C, Burgdorf J (1999) Paradoxical effects of serotonin and opioids in pemoline-induced self-injurious behavior. Pharmacol Biochem Behav 63:361–366

    CAS  Google Scholar 

  148. Yuan X, Devine DP (2016) The role of anxiety in vulnerability for self-injurious behaviour: studies in a rodent model. Behav Brain Res 311:201–209

    CAS  Google Scholar 

  149. Muehlmann AM, Brown BD, Devine DP (2008) Pemoline-induced self-injurious behavior: a rodent model of pharmacotherapeutic efficacy. J Pharmacol Exp Ther 324:214–223

    CAS  Google Scholar 

  150. Muehlmann AM, Devine DP (2008) Self-injurious behavior: individual differences in neurotransmitter concentrations using an animal model. Keystone Symposium: Towards Identifying the Pathophysiology of Autistic Syndromes. C2:104

    Google Scholar 

  151. Muehlmann AM, Devine DP (2008) Glutamate-mediated neuroplasticity in an animal model of self-injurious behaviour. Behav Brain Res 189:32–40

    CAS  Google Scholar 

  152. Soderling TR, Derkach VA (2000) Postsynaptic protein phosphorylation and LTP. Trends Neurosci 23:75–80

    CAS  PubMed  Google Scholar 

  153. Barnes CA, Danysz W, Parsons CG (1996) Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats. Eur J Neurosci 8:565–571

    CAS  PubMed  Google Scholar 

  154. Chen HS, Wang YF, Rayudu PV, Edgecomb P, Neill JC, Segal MM, Lipton SA, Jensen FE (1998) Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience 86:1121–1132

    CAS  PubMed  Google Scholar 

  155. Muehlmann AM, Wilkinson JA, Devine DP (2011) Individual differences in vulnerability for self-injurious behavior: studies using an animal model. Behav Brain Res 217:148–154

    Google Scholar 

  156. Stead JDH, Clinton S, Neal C, Schneider J, Jama A, Miller S, Vazquez DM, Watson SJ, Akil H (2006) Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors. Behav Genet 36:697–712

    PubMed  Google Scholar 

  157. Kabbaj M, Devine DP, Savage VR, Akil H (2000) Neurobiological correlates of individual differences in novelty-seeking behavior in the rat: differential expression of stress-related molecules. J Neurosci 20:6983–6986

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Evans AK, Lowry CA (2007) Pharmacology of the beta-carboline FG-7,142, a partial inverse agonist at the benzodiazepine allosteric site of the GABA A receptor: neurochemical, neurophysiological, and behavioral effects. CNS Drug Rev 13:475–501

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Muehlmann AM, Kies SD, Turner CA, Wolfman S, Lewis MH, Devine DP (2012) Self-injurious behavior: limbic dysregulation and stress effects in an animal model. J Intellect Disabil Res 56:490–500

    CAS  PubMed  Google Scholar 

  160. Devine DP, Muehlmann AM (2009) Tiermodelle für selbstverletzendes Verhalten (Animal models of self-injurious behavior). In: Schmahl C, Stiglmayr C (eds) Selbstverletzendes Verhalten bei Stressassoziierten Erkrankungen (Self-injurious behaviour in stress-associated disorders). Verlag W. Kohlhammer, Stuttgart, Germany, pp 39–60

    Google Scholar 

  161. Bloom CM, Holly S, Miller AM (2012) Self-injurious behavior vs. nonsuicidal self-injury, the CNS stimulant pemoline as a model of self-destructive behavior. Crisis 33:106–112

    PubMed  Google Scholar 

  162. Kasim S, Jinnah HA (2003) Self-biting induced by activation of L-type calcium channels in mice: dopaminergic influences. Dev Neurosci 25:20–25

    CAS  PubMed  Google Scholar 

  163. Kasim S, Egami K, Jinnah HA (2002) Self-biting induced by activation of L-type calcium channels in mice: serotonergic influences. Dev Neurosci 24:322–327

    CAS  PubMed  Google Scholar 

  164. Jinnah HA, Yitta S, Drew T, Kim BS, Visser JE, Rothstein JD (1999) Calcium channel activation and self-biting in mice. Proc Natl Acad Sci U S A 96:15228–15232

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Kasim S, Blake BL, Fan X, Chartoff E, Egami K, Breese GR, Hess EJ, Jinnah HA (2006) The role of dopamine receptors in the neurobehavioral syndrome provoked by activation of L-type calcium channels in rodents. Dev Neurosci 28:505517

    Google Scholar 

  166. Hooper M, Hardy K, Handyside A, Hunter S, Monk M (1987) HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326:292–295

    CAS  PubMed  Google Scholar 

  167. Kuehn MR, Bradley A, Robertson EJ, Evans MJ (1987) A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326:295–298

    CAS  PubMed  Google Scholar 

  168. Jinnah HA, Hess EJ, Wilson MC, Gage FH, Friedmann T (1992) Localization of hypoxanthine-guanine phosphoribosyltransferase mRNA in the mouse brain by in situ hybridization. Mol Cell Neurosci 3:64–78

    CAS  PubMed  Google Scholar 

  169. Jinnah HA, Page T, Friedmann T (1993) Brain purines in a genetic mouse model of Lesch-Nyhan disease. J Neurochem 60:2036–2045

    CAS  PubMed  Google Scholar 

  170. Dunnett SB, Sirinathsinghji DJ, Heavens R, Rogers DC, Kuehn MR (1989) Monoamine deficiency in a transgenic (Hprt-) mouse model of Lesch-Nyhan syndrome. Brain Res 501:401–406

    CAS  PubMed  Google Scholar 

  171. Finger S, Heavens RP, Sirinathsinghji DJS, Kuehn MR, Dunnett SB (1988) Behavioral and neurochemical evaluation of a transgenic mouse model of Lesch-Nyhan syndrome. J Neurol Sci 86:203–213

    CAS  PubMed  Google Scholar 

  172. Jinnah HA, Wojcik BE, Hunt M, Narang N, Lee KY, Goldstein M, Wamsley JK, Langlais PJ, Friedmann T (1994) Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease. J Neurosci 14:1164–1175

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Engle SJ, Womer DE, Davies PM, Boivin G, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA (1996) HPRT-APRT-deficient mice are not a model for Lesch-Nyhan syndrome. Hum Mol Genet 5:1607–1610

    CAS  PubMed  Google Scholar 

  174. Kasim S, Jinnah HA (2002) Pharmacologic thresholds for self-injurious behavior in a genetic mouse model of Lesch-Nyhan disease. Pharmacol Biochem Behav 73:583–592

    CAS  Google Scholar 

  175. Razzak A, Fujiwara M, Oishi MR, Ueki S (1977) Possible involvement of a central noradrenergic system in automutilation induced by clonidine in mice. Jpn J Pharmacol 27:145–152

    CAS  PubMed  Google Scholar 

  176. Bhattacharya SK, Jaiswal AK, Mukhopadhyay M, Datla KP (1988) Clonidine-induced automutilation in mice as a laboratory model for clinical self-injurious behaviour. J Psychiatr Res 22:43–50

    CAS  PubMed  Google Scholar 

  177. Keebaugh AC, Mitchell HA, Gaval-Cruz M, Freeman KG, Edwards GL, Weinshenker D, Thomas JW (2011) PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. PLoS One 6:e22381

    CAS  PubMed  PubMed Central  Google Scholar 

  178. King BH, Au D, Poland RE (1993) Low dose naltrexone inhibits pemoline-induced self-biting behavior in prepubertal rats. J Child Adolsc Psychopharmacol 3:71–79

    CAS  Google Scholar 

  179. Rojahn J (1986) Self-injurious and stereotypic behavior of noninstitutionalized mentally retarded people: prevalence and classification. Am J Ment Defic 91:268–276

    CAS  PubMed  Google Scholar 

  180. Rojahn J (1984) Self-injurious behavior in institutionalized severely/profoundly retarded adults: prevalence data and staff agreement. J Behav Assess 6:13–27

    Google Scholar 

  181. Blake BL, Muehlmann AM, Egami K, Breese GR, Devine DP, Jinnah HA (2007) Nifedipine suppresses self-injurious behaviors in animals. Dev Neurosci 29:241–250

    CAS  Google Scholar 

  182. Criswell HE, Johnson KB, Mueller RA, Breese GR (1993) Evidence for involvement of brain dopamine and other mechanisms in the behavioral action of the N-methyl-D-aspartic acid antagonist MK-801 in control and 6-hydroxydopamine-lesioned rats. J Pharmacol Exp Ther 265:1001–1010

    CAS  Google Scholar 

  183. Ellison G (1995) The N-methyl-D-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Res Brain Res Rev 20:250–267

    CAS  PubMed  Google Scholar 

  184. Davanzo PA, King BH (1996) Open trial lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation. J Child Adolesc Psychopharmacol 6:273–279

    CAS  Google Scholar 

  185. Sasso DA, Kalanithi PS, Trueblood KV, Pittenger C, Kelmendi B, Wayslink S, Malison RT, Krystal JH, Coric V (2006) Beneficial effects of the glutamate-modulating agent riluzole on disordered eating and pathological skin-picking behaviors. J Clin Psychopharmacol 26:685–687

    Google Scholar 

  186. Pittenger C, Krystal JH, Coric V (2005) Initial evidence of the beneficial effects of glutamate-modulating agents in the treatment of self-injurious behavior associated with borderline personality disorder. J Clin Psychiatry 66:1492–1493

    Google Scholar 

  187. Rizvi ST (2002) Lamotrigine and borderline personality disorder. J Child Adolesc Psychopharmacol 12:365–366

    Google Scholar 

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Devine, D.P. (2019). Animal Models of Self-Injurious Behavior: An Update. In: Kobeissy, F. (eds) Psychiatric Disorders. Methods in Molecular Biology, vol 2011. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9554-7_3

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