Animal Models of ADHD

  • A. BariEmail author
  • T. W. Robbins
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 7)


Studies employing animal models of attention-deficit/hyperactivity disorder (ADHD) present clear inherent advantages over human studies. Animal models are invaluable tools for the study of underlying neurochemical, neuropathological and genetic alterations that cause ADHD, because they allow relatively fast, rigorous hypothesis testing and invasive manipulations as well as selective breeding. Moreover, especially for ADHD, animal models with good predictive validity would allow the assessment of potential new therapeutics. In this chapter, we describe and comment on the most frequently used animal models of ADHD that have been created by genetic, neurochemical and physical alterations in rodents. We then discuss that an emerging and promising direction of the field is the analysis of individual behavioural differences among a normal population of animals. Subjects presenting extreme characteristics related to ADHD can be studied, thereby avoiding some of the problems that are found in other models, such as functional recovery and unnecessary assumptions about aetiology. This approach is justified by the theoretical need to consider human ADHD as the extreme part of a spectrum of characteristics that are distributed normally in the general population, as opposed to the predominant view of ADHD as a separate pathological category.


ADHD Atomoxetine Attention Behavioural models Fronto-striatal loops Genetic models Hyperactivity Impulsivity Psychostimulants 



Five-choice serial reaction time task






Anterior cingulate cortex


Attention-deficit/hyperactivity disorder


Continuous performance task




Dopamine transporter


Dopamine transporter gene 1


Dopamine transporter knock-out




Dopamine receptor D4


Differential reinforcement of low rates of responding


Diagnostic and statistical manual of mental disorders 4th edition


Fixed consecutive number


Genetically hypertensive rat


International classification of diseases 10th revision


Infralimbic cortex


Lever-holding task






Nucleus accumbens


Naples high-excitability


Orbitofrontal cortex


Post-natal day


Prefrontal cortex


Prelimbic cortex


Spontaneously hypertensive rat


Synaptosomal-associated protein 25


Stop-signal reaction time


Stop-signal task

TRbeta 1

Thyroid hormone receptor beta 1




  1. Adams ZW, Derefinko KJ, Milich R, Fillmore MT (2008) Inhibitory functioning across ADHD subtypes: recent findings, clinical implications, and future directions. Dev Disabil Res Rev 14:268–275PubMedCrossRefGoogle Scholar
  2. Adriani W, Laviola G (2004) Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model. Behav Pharmacol 15:341–352PubMedCrossRefGoogle Scholar
  3. Adriani W, Caprioli A, Granstrem O, Carli M, Laviola G (2003) The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations. Neurosci Biobehav Rev 27:639–651PubMedCrossRefGoogle Scholar
  4. Alderson RM, Rapport MD, Kofler MJ (2007) Attention-deficit/hyperactivity disorder and behavioral inhibition: a meta-analytic review of the stop-signal paradigm. J Abnorm Child Psychol 35:745–758PubMedCrossRefGoogle Scholar
  5. Alexander GE, Crutcher MD, DeLong MR (1990) Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res 85:119–146PubMedCrossRefGoogle Scholar
  6. Alsop B (2007) Problems with spontaneously hypertensive rats (SHR) as a model of attention-deficit/hyperactivity disorder (AD/HD). J Neurosci Methods 162:42–48PubMedCrossRefGoogle Scholar
  7. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington DCGoogle Scholar
  8. Applegate B, Lahey BB, Hart EL, Biederman J, Hynd GW, Barkley RA, Ollendick T, Frick PJ, Greenhill L, McBurnett K, Newcorn JH, Kerdyk L, Garfinkel B, Waldman I, Shaffer D (1997) Validity of the age-of-onset criterion for ADHD: a report from the DSM-IV field trials. J Am Acad Child Adolesc Psychiatry 36:1211–1221PubMedCrossRefGoogle Scholar
  9. Archer T, Danysz W, Fredriksson A, Jonsson G, Luthman J, Sundstrom E, Teiling A (1988a) Neonatal 6-hydroxydopamine-induced dopamine depletions: motor activity and performance in maze learning. Pharmacol Biochem Behav 31:357–364PubMedCrossRefGoogle Scholar
  10. Archer T, Fredriksson A, Sundstrom E, Luthman J, Lewander T, Soderberg U, Jonsson G (1988b) Prenatal methylazoxymethanol treatment potentiates d-amphetamine- and methylphenidate-induced motor activity in male and female rats. Pharmacol Toxicol 63:233–239PubMedCrossRefGoogle Scholar
  11. Aspide R, Gironi Carnevale UA, Sergeant JA, Sadile AG (1998) Non-selective attention and nitric oxide in putative animal models of attention-deficit hyperactivity disorder. Behav Brain Res 95:123–133PubMedCrossRefGoogle Scholar
  12. Avale ME, Falzone TL, Gelman DM, Low MJ, Grandy DK, Rubinstein M (2004) The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder. Mol Psychiatry 9:718–726PubMedGoogle Scholar
  13. Avila C, Cuenca I, Felix V, Parcet MA, Miranda A (2004) Measuring impulsivity in school-aged boys and examining its relationship with ADHD and ODD ratings. J Abnorm Child Psychol 32:295–304PubMedCrossRefGoogle Scholar
  14. Barbelivien A, Ruotsalainen S, Sirvio J (2001) Metabolic alterations in the prefrontal and cingulate cortices are related to behavioral deficits in a rodent model of attention-deficit hyperactivity disorder. Cereb Cortex 11:1056–1063PubMedCrossRefGoogle Scholar
  15. Bari A, Dalley JW, Robbins TW (2008) The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats. Nat Protoc 3:759–767PubMedCrossRefGoogle Scholar
  16. Bari A, Eagle DM, Mar AC, Robinson ES, Robbins TW (2009) Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on stop task performance in rats. Psychopharmacology (Berl) 205:273–283CrossRefGoogle Scholar
  17. Barkley RA (1997a) Attention-deficit/hyperactivity disorder, self-regulation, and time: toward a more comprehensive theory. J Dev Behav Pediatr 18:271–279PubMedGoogle Scholar
  18. Barkley RA (1997b) Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull 121:65–94PubMedCrossRefGoogle Scholar
  19. Barkley RA, Biederman J (1997) Toward a broader definition of the age-of-onset criterion for attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 36:1204–1210PubMedCrossRefGoogle Scholar
  20. Barr CL, Feng Y, Wigg K, Bloom S, Roberts W, Malone M, Schachar R, Tannock R, Kennedy JL (2000) Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder. Mol Psychiatry 5:405–409PubMedCrossRefGoogle Scholar
  21. Barr AM, Lehmann-Masten V, Paulus M, Gainetdinov RR, Caron MG, Geyer MA (2004) The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice. Neuropsychopharmacology 29:221–228PubMedCrossRefGoogle Scholar
  22. Beck LH, Bransome ED Jr, Mirsky AF, Rosvold HE, Sarason I (1956) A continuous performance test of brain damage. J Consult Psychol 20:343–350PubMedCrossRefGoogle Scholar
  23. Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ (2008) High impulsivity predicts the switch to compulsive cocaine-taking. Science 320:1352–1355PubMedCrossRefGoogle Scholar
  24. Bendel P, Eilam R (1992) Quantitation of ventricular size in normal and spontaneously hypertensive rats by magnetic resonance imaging. Brain Res 574:224–228PubMedCrossRefGoogle Scholar
  25. Bernal J (2002) Action of thyroid hormone in brain. J Endocrinol Invest 25:268–288PubMedGoogle Scholar
  26. Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57:1215–1220PubMedCrossRefGoogle Scholar
  27. Biederman J, Milberger S, Faraone SV, Kiely K, Guite J, Mick E, Ablon S, Warburton R, Reed E (1995) Family-environment risk factors for attention-deficit hyperactivity disorder. A test of Rutter’s indicators of adversity. Arch Gen Psychiatry 52:464–470PubMedCrossRefGoogle Scholar
  28. Bizarro L, Patel S, Murtagh C, Stolerman IP (2004) Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate. Behav Pharmacol 15:195–206PubMedGoogle Scholar
  29. Bizot JC, Chenault N, Houze B, Herpin A, David S, Pothion S, Trovero F (2007) Methylphenidate reduces impulsive behaviour in juvenile Wistar rats, but not in adult Wistar, SHR and WKY rats. Psychopharmacology (Berl) 193:215–223CrossRefGoogle Scholar
  30. Blondeau C, Dellu-Hagedorn F (2007) Dimensional analysis of ADHD subtypes in rats. Biol Psychiatry 61:1340–1350PubMedCrossRefGoogle Scholar
  31. Boonstra AM, Kooij JJ, Oosterlaan J, Sergeant JA, Buitelaar JK (2005) Does methylphenidate improve inhibition and other cognitive abilities in adults with childhood-onset ADHD? J Clin Exp Neuropsychol 27:278–298PubMedCrossRefGoogle Scholar
  32. Bradley C (1937) The behavior of children receiving benzedrine. Am J Psychiatry 9:577–585Google Scholar
  33. Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP (2006) Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904–1909PubMedGoogle Scholar
  34. Broersen LM, Uylings HB (1999) Visual attention task performance in Wistar and Lister hooded rats: response inhibition deficits after medial prefrontal cortex lesions. Neuroscience 94:47–57PubMedCrossRefGoogle Scholar
  35. Bruno KJ, Freet CS, Twining RC, Egami K, Grigson PS, Hess EJ (2007) Abnormal latent inhibition and impulsivity in coloboma mice, a model of ADHD. Neurobiol Dis 25:206–216PubMedCrossRefGoogle Scholar
  36. Bull E, Reavill C, Hagan JJ, Overend P, Jones DN (2000) Evaluation of the spontaneously hypertensive rat as a model of attention deficit hyperactivity disorder: acquisition and performance of the DRL-60s test. Behav Brain Res 109:27–35PubMedCrossRefGoogle Scholar
  37. Bushnell PJ (1998) Behavioral approaches to the assessment of attention in animals. Psychopharmacology (Berl) 138:231–259CrossRefGoogle Scholar
  38. Button TM, Thapar A, McGuffin P (2005) Relationship between antisocial behaviour, attention-deficit hyperactivity disorder and maternal prenatal smoking. Br J Psychiatry 187:155–160PubMedCrossRefGoogle Scholar
  39. Cardinal RN, Pennicott DR, Sugathapala CL, Robbins TW, Everitt BJ (2001) Impulsive choice induced in rats by lesions of the nucleus accumbens core. Science 292:2499–2501PubMedCrossRefGoogle Scholar
  40. Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9:361–380PubMedCrossRefGoogle Scholar
  41. Castellanos FX, Sonuga-Barke EJ, Milham MP, Tannock R (2006) Characterizing cognition in ADHD: beyond executive dysfunction. Trends Cogn Sci 10:117–123PubMedCrossRefGoogle Scholar
  42. Chamberlain SR, Muller U, Blackwell AD, Clark L, Robbins TW, Sahakian BJ (2006) Neurochemical modulation of response inhibition and probabilistic learning in humans. Science 311:861–863PubMedCrossRefGoogle Scholar
  43. Chamberlain SR, Del Campo N, Dowson J, Muller U, Clark L, Robbins TW, Sahakian BJ (2007) Atomoxetine improved response inhibition in adults with attention deficit/hyperactivity disorder. Biol Psychiatry 62:977–984PubMedCrossRefGoogle Scholar
  44. Chan E, Mattingley JB, Huang-Pollock C, English T, Hester R, Vance A, Bellgrove MA (2009) Abnormal spatial asymmetry of selective attention in ADHD. J Child Psychol Psychiatry 50:1064–1072PubMedCrossRefGoogle Scholar
  45. Cheon KA, Ryu YH, Kim YK, Namkoong K, Kim CH, Lee JD (2003) Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity disorder. Eur J Nucl Med Mol Imaging 30:306–311PubMedCrossRefGoogle Scholar
  46. Christakou A, Robbins TW, Everitt BJ (2004) Prefrontal cortical-ventral striatal interactions involved in affective modulation of attentional performance: implications for corticostriatal circuit function. J Neurosci 24:773–780PubMedCrossRefGoogle Scholar
  47. Chudasama Y, Passetti F, Rhodes SE, Lopian D, Desai A, Robbins TW (2003) Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav Brain Res 146:105–119PubMedCrossRefGoogle Scholar
  48. Clatworthy PL, Lewis SJ, Brichard L, Hong YT, Izquierdo D, Clark L, Cools R, Aigbirhio FI, Baron JC, Fryer TD, Robbins TW (2009) Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory. J Neurosci 29:4690–4696PubMedCrossRefGoogle Scholar
  49. Cole BJ, Robbins TW (1987) Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions. Psychopharmacology (Berl) 91:458–466CrossRefGoogle Scholar
  50. Corkum PV, Siegel LS (1993) Is the continuous performance task a valuable research tool for use with children with attention-deficit-hyperactivity disorder? J Child Psychol Psychiatry 34:1217–1239PubMedCrossRefGoogle Scholar
  51. Dalley JW, Fryer TD, Brichard L, Robinson ES, Theobald DE, Laane K, Pena Y, Murphy ER, Shah Y, Probst K, Abakumova I, Aigbirhio FI, Richards HK, Hong Y, Baron JC, Everitt BJ, Robbins TW (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315:1267–1270PubMedCrossRefGoogle Scholar
  52. Dalton GL, Lee MD, Kennett GA, Dourish CT, Clifton PG (2004) mCPP-induced hyperactivity in 5-HT2C receptor mutant mice is mediated by activation of multiple 5-HT receptor subtypes. Neuropharmacology 46:663–671PubMedCrossRefGoogle Scholar
  53. Daugherty TK, Quay HC (1991) Response perseveration and delayed responding in childhood behavior disorders. J Child Psychol Psychiatry 32:453–461PubMedCrossRefGoogle Scholar
  54. Davids E, Zhang K, Kula NS, Tarazi FI, Baldessarini RJ (2002) Effects of norepinephrine and serotonin transporter inhibitors on hyperactivity induced by neonatal 6-hydroxydopamine lesioning in rats. J Pharmacol Exp Ther 301:1097–1102PubMedCrossRefGoogle Scholar
  55. Davids E, Zhang K, Tarazi FI, Baldessarini RJ (2003) Animal models of attention-deficit hyperactivity disorder. Brain Res Brain Res Rev 42:1–21PubMedCrossRefGoogle Scholar
  56. de Villiers AS, Russell VA, Sagvolden T, Searson A, Jaffer A, Taljaard JJ (1995) Alpha 2-adrenoceptor mediated inhibition of [3H]dopamine release from nucleus accumbens slices and monoamine levels in a rat model for attention-deficit hyperactivity disorder. Neurochem Res 20:427–433PubMedCrossRefGoogle Scholar
  57. Dell’Anna ME, Calzolari S, Molinari M, Iuvone L, Calimici R (1991) Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats. Behav Brain Res 45:125–134PubMedCrossRefGoogle Scholar
  58. Dell’Anna ME, Luthman J, Lindqvist E, Olson L (1993) Development of monoamine systems after neonatal anoxia in rats. Brain Res Bull 32:159–170PubMedCrossRefGoogle Scholar
  59. Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ (1999) Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet 354:2132–2133PubMedCrossRefGoogle Scholar
  60. Eagle DM, Robbins TW (2003) Inhibitory control in rats performing a stop-signal reaction-time task: effects of lesions of the medial striatum and d-amphetamine. Behav Neurosci 117:1302–1317PubMedCrossRefGoogle Scholar
  61. Eagle DM, Tufft MR, Goodchild HL, Robbins TW (2007) Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol. Psychopharmacology (Berl) 192:193–206CrossRefGoogle Scholar
  62. Eagle DM, Bari A, Robbins TW (2008a) The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks. Psychopharmacology (Berl) 199:439–456CrossRefGoogle Scholar
  63. Eagle DM, Baunez C, Hutcheson DM, Lehmann O, Shah AP, Robbins TW (2008b) Stop-signal reaction-time task performance: role of prefrontal cortex and subthalamic nucleus. Cereb Cortex 18:178–188PubMedCrossRefGoogle Scholar
  64. Eagle DM, Lehmann O, Theobald DE, Pena Y, Zakaria R, Ghosh R, Dalley JW, Robbins TW (2009) Serotonin depletion impairs waiting but not stop-signal reaction time in rats: implications for theories of the role of 5-HT in behavioral inhibition. Neuropsychopharmacology 34:1311–1321PubMedCrossRefGoogle Scholar
  65. Elliott R, Sahakian BJ, Matthews K, Bannerjea A, Rimmer J, Robbins TW (1997) Effects of methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology (Berl) 131:196–206CrossRefGoogle Scholar
  66. Evenden JL (1998) The pharmacology of impulsive behaviour in rats III: the effects of amphetamine, haloperidol, imipramine, chlordiazepoxide and ethanol on a paced fixed consecutive number schedule. Psychopharmacology (Berl) 138:295–304CrossRefGoogle Scholar
  67. Evenden JL (1999) Varieties of impulsivity. Psychopharmacology (Berl) 146:348–361CrossRefGoogle Scholar
  68. Fahlke C, Hansen S (1999) Alcohol responsiveness, hyperreactivity, and motor restlessness in an animal model for attention-deficit hyperactivity disorder. Psychopharmacology (Berl) 146:1–9CrossRefGoogle Scholar
  69. Fan X, Xu M, Hess EJ (2010) D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD. Neurobiol Dis 37:228–236Google Scholar
  70. Faraone SV, Biederman J (1998) Neurobiology of attention-deficit hyperactivity disorder. Biol Psychiatry 44:951–958PubMedCrossRefGoogle Scholar
  71. Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158:1052–1057PubMedCrossRefGoogle Scholar
  72. Faraone SV, Sergeant J, Gillberg C, Biederman J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2:104–113PubMedGoogle Scholar
  73. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1313–1323PubMedCrossRefGoogle Scholar
  74. Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R, Roberts W, Malone M, Swanson J, Kennedy JL, Barr CL (2005) The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder. Mol Psychiatry 10(998–1005):973CrossRefGoogle Scholar
  75. Feola TW, de Wit H, Richards JB (2000) Effects of d-amphetamine and alcohol on a measure of behavioral inhibition in rats. Behav Neurosci 114:838–848PubMedCrossRefGoogle Scholar
  76. Ferguson SA (1996) Neuroanatomical and functional alterations resulting from early postnatal cerebellar insults in rodents. Pharmacol Biochem Behav 55:663–671PubMedCrossRefGoogle Scholar
  77. Ferguson SA, Paule MG (1996) Effects of chlorpromazine and diazepam on time estimation behavior and motivation in rats. Pharmacol Biochem Behav 53:115–122PubMedCrossRefGoogle Scholar
  78. Ferguson SA, Paule MG, Holson RR (1996) Functional effects of methylazoxymethanol-induced cerebellar hypoplasia in rats. Neurotoxicol Teratol 18:529–537PubMedCrossRefGoogle Scholar
  79. Ferguson SA, Paule MG, Holson RR (2001) Neonatal dexamethasone on day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits. Neurotoxicol Teratol 23:57–69PubMedCrossRefGoogle Scholar
  80. Ferster CB, Skinner BF (1957) Schedules of reinforcement. Appleton-Century-Crofts, New YorkCrossRefGoogle Scholar
  81. Festing MF, Bender K (1984) Genetic relationships between inbred strains of rats. An analysis based on genetic markers at 28 biochemical loci. Genet Res 44:271–281PubMedCrossRefGoogle Scholar
  82. Filipek PA, Semrud-Clikeman M, Steingard RJ, Renshaw PF, Kennedy DN, Biederman J (1997) Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology 48:589–601PubMedCrossRefGoogle Scholar
  83. Fineberg NA, Potenza MN, Chamberlain SR, Berlin HA, Menzies L, Bechara A, Sahakian BJ, Robbins TW, Bullmore ET, Hollander E (2009) Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology 35(3):591–604Google Scholar
  84. Fox AT, Hand DJ, Reilly MP (2008) Impulsive choice in a rodent model of attention-deficit/hyperactivity disorder. Behav Brain Res 187:146–152PubMedCrossRefGoogle Scholar
  85. Fung YK, Lau YS (1989) Effects of prenatal nicotine exposure on rat striatal dopaminergic and nicotinic systems. Pharmacol Biochem Behav 33:1–6PubMedCrossRefGoogle Scholar
  86. Gainetdinov RR, Caron MG (2000) An animal model of attention deficit hyperactivity disorder. Mol Med Today 6:43–44PubMedCrossRefGoogle Scholar
  87. Gainetdinov RR, Caron MG (2001) Genetics of childhood disorders: XXIV. ADHD, part 8: Hyperdopaminergic mice as an animal model of ADHD. J Am Acad Child Adolesc Psychiatry 40:380–382PubMedCrossRefGoogle Scholar
  88. Gainetdinov RR, Jones SR, Fumagalli F, Wightman RM, Caron MG (1998) Re-evaluation of the role of the dopamine transporter in dopamine system homeostasis. Brain Res Brain Res Rev 26:148–153PubMedCrossRefGoogle Scholar
  89. Gainetdinov RR, Jones SR, Caron MG (1999a) Functional hyperdopaminergia in dopamine transporter knock-out mice. Biol Psychiatry 46:303–311PubMedCrossRefGoogle Scholar
  90. Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG (1999b) Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283:397–401PubMedCrossRefGoogle Scholar
  91. Giedd JN, Blumenthal J, Molloy E, Castellanos FX (2001) Brain imaging of attention deficit/hyperactivity disorder. Ann N Y Acad Sci 931:33–49PubMedCrossRefGoogle Scholar
  92. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612PubMedCrossRefGoogle Scholar
  93. Gjone H, Stevenson J, Sundet JM (1996) Genetic influence on parent-reported attention-related problems in a Norwegian general population twin sample. J Am Acad Child Adolesc Psychiatry 35:588–596; discussion 596–598Google Scholar
  94. Gordon M (1979) The assessment of impulsivity and mediating behaviors in hyperactive and nonhyperactive boys. J Abnorm Child Psychol 7:317–326PubMedCrossRefGoogle Scholar
  95. Gorenstein EE, Newman JP (1980) Disinhibitory psychopathology: a new perspective and a model for research. Psychol Rev 87:301–315PubMedCrossRefGoogle Scholar
  96. Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedCrossRefGoogle Scholar
  97. Granon S, Changeux JP (2006) Attention-deficit/hyperactivity disorder: a plausible mouse model? Acta Paediatr 95:645–649PubMedCrossRefGoogle Scholar
  98. Granon S, Hardouin J, Courtier A, Poucet B (1998) Evidence for the involvement of the rat prefrontal cortex in sustained attention. Q J Exp Psychol B 51:219–233PubMedGoogle Scholar
  99. Granon S, Passetti F, Thomas KL, Dalley JW, Everitt BJ, Robbins TW (2000) Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into rat prefrontal cortex. J Neurosci 20:1208–1215PubMedGoogle Scholar
  100. Granon S, Faure P, Changeux JP (2003) Executive and social behaviors under nicotinic receptor regulation. Proc Natl Acad Sci USA 100:9596–9601PubMedCrossRefGoogle Scholar
  101. Hand DJ, Fox AT, Reilly MP (2009) Differential effects of d-amphetamine on impulsive choice in spontaneously hypertensive and Wistar-Kyoto rats. Behav Pharmacol 20:549–553PubMedCrossRefGoogle Scholar
  102. Hanna GL, Ornitz EM, Hariharan M (1996) Urinary catecholamine excretion and behavioral differences in ADHD and normal boys. J Child Adolesc Psychopharmacol 6:63–73PubMedCrossRefGoogle Scholar
  103. Harrison AA, Everitt BJ, Robbins TW (1997) Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms. Psychopharmacology (Berl) 133:329–342CrossRefGoogle Scholar
  104. Hausknecht KA, Acheson A, Farrar AM, Kieres AK, Shen RY, Richards JB, Sabol KE (2005) Prenatal alcohol exposure causes attention deficits in male rats. Behav Neurosci 119:302–310PubMedCrossRefGoogle Scholar
  105. Heal DJ, Smith SL, Kulkarni RS, Rowley HL (2008) New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD. Pharmacol Biochem Behav 90:184–197PubMedCrossRefGoogle Scholar
  106. Helms CM, Gubner NR, Wilhelm CJ, Mitchell SH, Grandy DK (2008) D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking. Pharmacol Biochem Behav 90:387–393PubMedCrossRefGoogle Scholar
  107. Hess EJ, Collins KA, Wilson MC (1996) Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. J Neurosci 16:3104–3111PubMedGoogle Scholar
  108. Highfield DA, Hu D, Amsel A (1998) Alleviation of x-irradiation-based deficit in memory-based learning by D-amphetamine: suggestions for attention deficit-hyperactivity disorder. Proc Natl Acad Sci USA 95:5785–5788PubMedCrossRefGoogle Scholar
  109. Holson RR, Gazzara RA, Ferguson SA, Adams J (1997) Behavioral effects of low-dose gestational day 11-13 retinoic acid exposure. Neurotoxicol Teratol 19:355–362PubMedCrossRefGoogle Scholar
  110. Huang-Pollock CL, Nigg JT (2003) Searching for the attention deficit in attention deficit hyperactivity disorder: the case of visuospatial orienting. Clin Psychol Rev 23:801–830PubMedCrossRefGoogle Scholar
  111. Huang-Pollock CL, Nigg JT, Carr TH (2005) Deficient attention is hard to find: applying the perceptual load model of selective attention to attention deficit hyperactivity disorder subtypes. J Child Psychol Psychiatry 46:1211–1218PubMedCrossRefGoogle Scholar
  112. Hudziak JJ, Heath AC, Madden PF, Reich W, Bucholz KK, Slutske W, Bierut LJ, Neuman RJ, Todd RD (1998) Latent class and factor analysis of DSM-IV ADHD: a twin study of female adolescents. J Am Acad Child Adolesc Psychiatry 37:848–857PubMedCrossRefGoogle Scholar
  113. Iuvone L, Geloso MC, Dell’Anna E (1996) Changes in open field behavior, spatial memory, and hippocampal parvalbumin immunoreactivity following enrichment in rats exposed to neonatal anoxia. Exp Neurol 139:25–33PubMedCrossRefGoogle Scholar
  114. Johansen EB, Aase H, Meyer A, Sagvolden T (2002) Attention-deficit/hyperactivity disorder (ADHD) behaviour explained by dysfunctioning reinforcement and extinction processes. Behav Brain Res 130:37–45PubMedCrossRefGoogle Scholar
  115. Johansen EB, Sagvolden T, Kvande G (2005) Effects of delayed reinforcers on the behavior of an animal model of attention-deficit/hyperactivity disorder (ADHD). Behav Brain Res 162:47–61PubMedCrossRefGoogle Scholar
  116. Johansen EB, Killeen PR, Sagvolden T (2007) Behavioral variability, elimination of responses, and delay-of-reinforcement gradients in SHR and WKY rats. Behav Brain Funct 3:60PubMedCrossRefGoogle Scholar
  117. Johnson ML, Ely DL, Turner ME (1992) Genetic divergence between the Wistar-Kyoto rat and the spontaneously hypertensive rat. Hypertension 19:425–427PubMedCrossRefGoogle Scholar
  118. Johnson KA, Robertson IH, Barry E, Mulligan A, Daibhis A, Daly M, Watchorn A, Gill M, Bellgrove MA (2008) Impaired conflict resolution and alerting in children with ADHD: evidence from the Attention Network Task (ANT). J Child Psychol Psychiatry 49:1339–1347PubMedCrossRefGoogle Scholar
  119. Jones MD, Hess EJ (2003) Norepinephrine regulates locomotor hyperactivity in the mouse mutant coloboma. Pharmacol Biochem Behav 75:209–216PubMedCrossRefGoogle Scholar
  120. Jones MD, Williams ME, Hess EJ (2001a) Abnormal presynaptic catecholamine regulation in a hyperactive SNAP-25-deficient mouse mutant. Pharmacol Biochem Behav 68:669–676PubMedCrossRefGoogle Scholar
  121. Jones MD, Williams ME, Hess EJ (2001b) Expression of catecholaminergic mRNAs in the hyperactive mouse mutant coloboma. Brain Res Mol Brain Res 96:114–121PubMedCrossRefGoogle Scholar
  122. Jucaite A, Fernell E, Halldin C, Forssberg H, Farde L (2005) Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity. Biol Psychiatry 57:229–238PubMedCrossRefGoogle Scholar
  123. Kipp K (2005) A developmental perspective on the measurement of cognitive deficits in attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1256–1260PubMedCrossRefGoogle Scholar
  124. Kostrzewa RM, Kostrzewa JP, Kostrzewa RA, Nowak P, Brus R (2008) Pharmacological models of ADHD. J Neural Transm 115:287–298PubMedCrossRefGoogle Scholar
  125. Kraemer HC, Noda A, O’Hara R (2004) Categorical versus dimensional approaches to diagnosis: methodological challenges. J Psychiatr Res 38:17–25PubMedCrossRefGoogle Scholar
  126. Krause KH, Dresel SH, Krause J, Kung HF, Tatsch K (2000) Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: effects of methylphenidate as measured by single photon emission computed tomography. Neurosci Lett 285:107–110PubMedCrossRefGoogle Scholar
  127. Kupietz SS, Balka EB (1976) Alterations in the vigilance performance of children receiving amitriptyline and methylphenidate pharmacotherapy. Psychopharmacology (Berl) 50:29–33CrossRefGoogle Scholar
  128. Kurtz TW, Morris RC Jr (1987) Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat. Hypertension 10:127–131PubMedCrossRefGoogle Scholar
  129. Kustanovich V, Merriman B, McGough J, McCracken JT, Smalley SL, Nelson SF (2003) Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder. Mol Psychiatry 8:309–315PubMedCrossRefGoogle Scholar
  130. Lahey BB, Applegate B (2001) Validity of DSM-IV ADHD. J Am Acad Child Adolesc Psychiatry 40:502–504PubMedCrossRefGoogle Scholar
  131. LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL (1996) Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry 1:121–124PubMedGoogle Scholar
  132. Lawrence CA, Barry RJ, Clarke AR, Johnstone SJ, McCarthy R, Selikowitz M, Broyd SJ (2005) Methylphenidate effects in attention deficit/hyperactivity disorder: electrodermal and ERP measures during a continuous performance task. Psychopharmacology (Berl) 183:81–91CrossRefGoogle Scholar
  133. Le Moal M, Galey D, Cardo B (1975) Behavioral effects of local injection of 6-hydroxydopamine in the medial ventral tegmentum in the rat. Possible role of the mesolimbic dopamingergic system. Brain Res 88:190–194PubMedCrossRefGoogle Scholar
  134. Leo D, Sorrentino E, Volpicelli F, Eyman M, Greco D, Viggiano D, di Porzio U, Perrone-Capano C (2003) Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD. Neurosci Biobehav Rev 27:661–669PubMedCrossRefGoogle Scholar
  135. Levin ED, Rezvani AH (2002) Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord 1:423–431PubMedCrossRefGoogle Scholar
  136. Levy F, Hay DA, McStephen M, Wood C, Waldman I (1997) Attention-deficit hyperactivity disorder: a category or a continuum? Genetic analysis of a large-scale twin study. J Am Acad Child Adolesc Psychiatry 36:737–744PubMedCrossRefGoogle Scholar
  137. Lijffijt M, Kenemans JL, Verbaten MN, van Engeland H (2005) A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control? J Abnorm Psychol 114:216–222PubMedCrossRefGoogle Scholar
  138. Lim MH, Kim HW, Paik KC, Cho SC, Yoon DY, Lee HJ (2006) Association of the DAT1 polymorphism with attention deficit hyperactivity disorder (ADHD): a family-based approach. Am J Med Genet B Neuropsychiatr Genet 141B:309–311PubMedCrossRefGoogle Scholar
  139. Linnet KM, Dalsgaard S, Obel C, Wisborg K, Henriksen TB, Rodriguez A, Kotimaa A, Moilanen I, Thomsen PH, Olsen J, Jarvelin MR (2003) Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence. Am J Psychiatry 160:1028–1040PubMedCrossRefGoogle Scholar
  140. Linthorst AC, De Lang H, De Jong W, Versteeg DH (1991) Effect of the dopamine D2 receptor agonist quinpirole on the in vivo release of dopamine in the caudate nucleus of hypertensive rats. Eur J Pharmacol 201:125–133PubMedCrossRefGoogle Scholar
  141. Logan GD (1994) On the ability to inhibit thought and action. A users’ guide to the stop signal paradigm. In: Dagenbach D, Carr TH (eds) Inhibitory processes in attention, memory and language. Academic, San Diego, CA, pp 189–236Google Scholar
  142. Logan GD, Cowan WB, Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform 10:276–291PubMedCrossRefGoogle Scholar
  143. Losier BJ, McGrath PJ, Klein RM (1996) Error patterns on the continuous performance test in non-medicated and medicated samples of children with and without ADHD: a meta-analytic review. J Child Psychol Psychiatry 37:971–987PubMedCrossRefGoogle Scholar
  144. Lou HC (1996) Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatr 85:1266–1271PubMedCrossRefGoogle Scholar
  145. Lubke GH, Muthen B, Moilanen IK, McGough JJ, Loo SK, Swanson JM, Yang MH, Taanila A, Hurtig T, Jarvelin MR, Smalley SL (2007) Subtypes versus severity differences in attention-deficit/hyperactivity disorder in the Northern Finnish Birth Cohort. J Am Acad Child Adolesc Psychiatry 46:1584–1593PubMedCrossRefGoogle Scholar
  146. Lubke GH, Hudziak JJ, Derks EM, van Bijsterveldt TC, Boomsma DI (2009) Maternal ratings of attention problems in ADHD: evidence for the existence of a continuum. J Am Acad Child Adolesc Psychiatry 48:1085–1093PubMedCrossRefGoogle Scholar
  147. Luders E, Narr KL, Hamilton LS, Phillips OR, Thompson PM, Valle JS, Del'Homme M, Strickland T, McCracken JT, Toga AW, Levitt JG (2009) Decreased callosal thickness in attention-deficit/hyperactivity disorder. Biol Psychiatry 65:84–88PubMedCrossRefGoogle Scholar
  148. Luthman J, Fredriksson A, Lewander T, Jonsson G, Archer T (1989) Effects of d-amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment. Psychopharmacology (Berl) 99:550–557CrossRefGoogle Scholar
  149. Magara F, Ricceri L, Wolfer DP, Lipp HP (2000) The acallosal mouse strain I/LnJ: a putative model of ADHD? Neurosci Biobehav Rev 24:45–50PubMedCrossRefGoogle Scholar
  150. Mar AC, Robbins TW (2007) Delay discounting and impulsive choice in the rat. Curr Protoc Neurosci Chap. 8: Unit 8.22Google Scholar
  151. McClure GY, Wenger GR, McMillan DE (1997) Effects of drugs on response duration differentiation. V: differential effects under temporal response differentiation schedules. J Pharmacol Exp Ther 281:1357–1367PubMedGoogle Scholar
  152. McDonald MP, Wong R, Goldstein G, Weintraub B, Cheng SY, Crawley JN (1998) Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta1 receptor gene. Learn Mem 5:289–301PubMedGoogle Scholar
  153. McGaughy J, Turchi J, Sarter M (1994) Crossmodal divided attention in rats: effects of chlordiazepoxide and scopolamine. Psychopharmacology (Berl) 115:213–220CrossRefGoogle Scholar
  154. McKinney WT Jr, Bunney WE Jr (1969) Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry 21:240–248PubMedCrossRefGoogle Scholar
  155. Mick E, Biederman J, Faraone SV, Sayer J, Kleinman S (2002) Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy. J Am Acad Child Adolesc Psychiatry 41:378–385PubMedCrossRefGoogle Scholar
  156. Milberger S, Biederman J, Faraone SV, Jones J (1998) Further evidence of an association between maternal smoking during pregnancy and attention deficit hyperactivity disorder: findings from a high-risk sample of siblings. J Clin Child Psychol 27:352–358PubMedCrossRefGoogle Scholar
  157. Milich R, Balentine A, Lynam D (2001) ADHD combined type and ADHD predominantly inattentive type are distinct and unrelated disorders. Clin Psychol Sci Practice 8:463–488CrossRefGoogle Scholar
  158. Mill J (2007) Rodent models: utility for candidate gene studies in human attention-deficit hyperactivity disorder (ADHD). J Neurosci Methods 166:294–305PubMedCrossRefGoogle Scholar
  159. Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S, Taylor E, Asherson P (2002) Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder. Am J Med Genet 114:269–271PubMedCrossRefGoogle Scholar
  160. Mobini S, Body S, Ho MY, Bradshaw CM, Szabadi E, Deakin JF, Anderson IM (2002) Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement. Psychopharmacology (Berl) 160:290–298CrossRefGoogle Scholar
  161. Moser MB, Moser EI, Wultz B, Sagvolden T (1988) Component analyses differentiate between exploratory behaviour of spontaneously hypertensive rats and Wistar Kyoto rats in a two-compartment free-exploration open field. Scand J Psychol 29:200–206PubMedCrossRefGoogle Scholar
  162. Muir JL, Everitt BJ, Robbins TW (1994) AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function. J Neurosci 14:2313–2326PubMedGoogle Scholar
  163. Muir JL, Everitt BJ, Robbins TW (1996) The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task. Cereb Cortex 6:470–481PubMedCrossRefGoogle Scholar
  164. Muller U, Clark L, Lam ML, Moore RM, Murphy CL, Richmond NK, Sandhu RS, Wilkins IA, Menon DK, Sahakian BJ, Robbins TW (2005) Lack of effects of guanfacine on executive and memory functions in healthy male volunteers. Psychopharmacology (Berl) 182:205–213CrossRefGoogle Scholar
  165. Navarra R, Graf R, Huang Y, Logue S, Comery T, Hughes Z, Day M (2008) Effects of atomoxetine and methylphenidate on attention and impulsivity in the 5-choice serial reaction time test. Prog Neuropsychopharmacol Biol Psychiatry 32(1):34–41PubMedCrossRefGoogle Scholar
  166. Neuman RJ, Sitdhiraksa N, Reich W, Ji TH, Joyner CA, Sun LW, Todd RD (2005) Estimation of prevalence of DSM-IV and latent class-defined ADHD subtypes in a population-based sample of child and adolescent twins. Twin Res Hum Genet 8:392–401PubMedCrossRefGoogle Scholar
  167. Nigg JT (2001) Is ADHD a disinhibitory disorder? Psychol Bull 127:571–598PubMedCrossRefGoogle Scholar
  168. Nigg JT (2005) Neuropsychologic theory and findings in attention-deficit/hyperactivity disorder: the state of the field and salient challenges for the coming decade. Biol Psychiatry 57:1424–1435PubMedCrossRefGoogle Scholar
  169. Nigg JT (2006) What causes ADHD? Understanding what goes wrong and why. Guilford, New York, USAGoogle Scholar
  170. Nigg JT, Knottnerus GM, Martel MM, Nikolas M, Cavanagh K, Karmaus W, Rappley MD (2008) Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control. Biol Psychiatry 63:325–331PubMedCrossRefGoogle Scholar
  171. Oades RD (1987) Attention deficit disorder with hyperactivity (ADDH): the contribution of catecholaminergic activity. Prog Neurobiol 29:365–391PubMedCrossRefGoogle Scholar
  172. Okamoto K, Aoki K (1963) Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27:282–293PubMedCrossRefGoogle Scholar
  173. Oosterlaan J, Logan GD, Sergeant JA (1998) Response inhibition in AD/HD, CD, comorbid AD/HD + CD, anxious, and control children: a meta-analysis of studies with the stop task. J Child Psychol Psychiatry 39:411–425PubMedCrossRefGoogle Scholar
  174. Orduna V, Valencia-Torres L, Bouzas A (2009) DRL performance of spontaneously hypertensive rats: dissociation of timing and inhibition of responses. Behav Brain Res 201:158–165PubMedCrossRefGoogle Scholar
  175. Pattij T, Janssen MC, Vanderschuren LJ, Schoffelmeer AN, van Gaalen MM (2007) Involvement of dopamine D1 and D2 receptors in the nucleus accumbens core and shell in inhibitory response control. Psychopharmacology (Berl) 191:587–598CrossRefGoogle Scholar
  176. Paz R, Barsness B, Martenson T, Tanner D, Allan AM (2007) Behavioral teratogenicity induced by nonforced maternal nicotine consumption. Neuropsychopharmacology 32:693–699PubMedCrossRefGoogle Scholar
  177. Pennington BF (2006) From single to multiple deficit models of developmental disorders. Cognition 101:385–413PubMedCrossRefGoogle Scholar
  178. Pennington BF, Ozonoff S (1996) Executive functions and developmental psychopathology. J Child Psychol Psychiatry 37:51–87PubMedCrossRefGoogle Scholar
  179. Polderman TJ, Derks EM, Hudziak JJ, Verhulst FC, Posthuma D, Boomsma DI (2007) Across the continuum of attention skills: a twin study of the SWAN ADHD rating scale. J Child Psychol Psychiatry 48:1080–1087PubMedCrossRefGoogle Scholar
  180. Pollier F, Sarre S, Aguerre S, Ebinger G, Mormede P, Michotte Y, Chaouloff F (2000) Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality. Neuropsychopharmacology 22:64–76PubMedCrossRefGoogle Scholar
  181. Puumala T, Ruotsalainen S, Jakala P, Koivisto E, Riekkinen P Jr, Sirvio J (1996) Behavioral and pharmacological studies on the validation of a new animal model for attention deficit hyperactivity disorder. Neurobiol Learn Mem 66:198–211PubMedCrossRefGoogle Scholar
  182. Quist JF, Barr CL, Schachar R, Roberts W, Malone M, Tannock R, Basile VS, Beitchman J, Kennedy JL (2000) Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 5:537–541PubMedCrossRefGoogle Scholar
  183. Rasmussen ER, Neuman RJ, Heath AC, Levy F, Hay DA, Todd RD (2004) Familial clustering of latent class and DSM-IV defined attention-deficit/hyperactivity disorder (ADHD) subtypes. J Child Psychol Psychiatry 45:589–598PubMedCrossRefGoogle Scholar
  184. Reja V, Goodchild AK, Phillips JK, Pilowsky PM (2002) Tyrosine hydroxylase gene expression in ventrolateral medulla oblongata of WKY and SHR: a quantitative real-time polymerase chain reaction study. Auton Neurosci 98:79–84PubMedCrossRefGoogle Scholar
  185. Richardson SA, Tizabi Y (1994) Hyperactivity in the offspring of nicotine-treated rats: role of the mesolimbic and nigrostriatal dopaminergic pathways. Pharmacol Biochem Behav 47:331–337PubMedCrossRefGoogle Scholar
  186. Rivalan M, Blondeau C, Dellu-Hagedorn F (2009) Modelling symptoms of mental disorders using a dimensional approach in the rat. In: Granon S (ed) Endophenotypes of psychiatric and neurodegenerative disorders in rodent models. Transworld Research Network, Trivandrum, pp 15–40Google Scholar
  187. Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl) 163:362–380CrossRefGoogle Scholar
  188. Robbins TW (2007) Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications. Philos Trans R Soc Lond B Biol Sci 362:917–932PubMedCrossRefGoogle Scholar
  189. Robbins TW, Everitt BJ, Marston HM, Wilkinson J, Jones GH, Page KJ (1989) Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes. Behav Brain Res 35:221–240PubMedCrossRefGoogle Scholar
  190. Robinson ES, Eagle DM, Mar AC, Bari A, Banerjee G, Jiang X, Dalley JW, Robbins TW (2008) Similar effects of the selective noradrenaline reuptake inhibitor atomoxetine on three distinct forms of impulsivity in the rat. Neuropsychopharmacology 33:1028–1037PubMedCrossRefGoogle Scholar
  191. Robinson ES, Eagle DM, Economidou D, Theobald DE, Mar AC, Murphy ER, Robbins TW, Dalley JW (2009) Behavioural characterisation of high impulsivity on the 5-choice serial reaction time task: specific deficits in ‘waiting’ versus ‘stopping’. Behav Brain Res 196:310–316PubMedCrossRefGoogle Scholar
  192. Rogers RD, Everitt BJ, Baldacchino A, Blackshaw AJ, Swainson R, Wynne K, Baker NB, Hunter J, Carthy T, Booker E, London M, Deakin JF, Sahakian BJ, Robbins TW (1999) Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20:322–339PubMedCrossRefGoogle Scholar
  193. Rogers RD, Baunez C, Everitt BJ, Robbins TW (2001) Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance. Behav Neurosci 115:799–811PubMedCrossRefGoogle Scholar
  194. Roman T, Schmitz M, Polanczyk GV, Eizirik M, Rohde LA, Hutz MH (2002) Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene. Am J Med Genet 114:154–158PubMedCrossRefGoogle Scholar
  195. Routh DK, Roberts RD (1972) Minimal brain dysfunction in children: failure to find evidence for a behavioral syndrome. Psychol Rep 31:307–314PubMedCrossRefGoogle Scholar
  196. Rubia K, Overmeyer S, Taylor E, Brammer M, Williams SC, Simmons A, Bullmore ET (1999) Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. Am J Psychiatry 156:891–896PubMedGoogle Scholar
  197. Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90:991–1001PubMedCrossRefGoogle Scholar
  198. Russell VA (2007) Neurobiology of animal models of attention-deficit hyperactivity disorder. J Neurosci Methods 161:185–198PubMedCrossRefGoogle Scholar
  199. Russell VA, Sagvolden T, Johansen EB (2005) Animal models of attention-deficit hyperactivity disorder. Behav Brain Funct 1:9PubMedCrossRefGoogle Scholar
  200. Sadile AG, Cerbone A, Grimaldi A, Manzi G, Cioffi LA (1986) Postnatal brain growth and behavior: evaluation of environmental factors. Bibl Nutr Dieta 38:194–205Google Scholar
  201. Sadile AG, Lamberti C, Siegfried B, Welzl H (1993) Circadian activity, nociceptive thresholds, nigrostriatal and mesolimbic dopaminergic activity in the Naples High- and Low-Excitability rat lines. Behav Brain Res 55:17–27PubMedCrossRefGoogle Scholar
  202. Sagvolden T (2000) Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit/hyperactivity disorder (AD/HD). Neurosci Biobehav Rev 24:31–39PubMedCrossRefGoogle Scholar
  203. Sagvolden T (2006) The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Behav Brain Funct 2:41PubMedCrossRefGoogle Scholar
  204. Sagvolden T, Metzger MA, Schiorbeck HK, Rugland AL, Spinnangr I, Sagvolden G (1992) The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants. Behav Neural Biol 58:103–112PubMedCrossRefGoogle Scholar
  205. Sagvolden T, Aase H, Zeiner P, Berger D (1998) Altered reinforcement mechanisms in attention-deficit/hyperactivity disorder. Behav Brain Res 94:61–71PubMedCrossRefGoogle Scholar
  206. Sagvolden T, Russell VA, Aase H, Johansen EB, Farshbaf M (2005) Rodent models of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1239–1247PubMedCrossRefGoogle Scholar
  207. Sanabria F, Killeen PR (2008) Evidence for impulsivity in the spontaneously hypertensive rat drawn from complementary response-withholding tasks. Behav Brain Funct 4:7PubMedCrossRefGoogle Scholar
  208. Sarter M, Hagan J, Dudchenko P (1992) Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part I. Psychopharmacology (Berl) 107:144–159CrossRefGoogle Scholar
  209. Schachar R, Mota VL, Logan GD, Tannock R, Klim P (2000) Confirmation of an inhibitory control deficit in attention-deficit/hyperactivity disorder. J Abnorm Child Psychol 28:227–235PubMedCrossRefGoogle Scholar
  210. Seidman LJ, Valera EM, Makris N (2005) Structural brain imaging of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1263–1272PubMedCrossRefGoogle Scholar
  211. Shaffer D, Greenhill L (1979) A critical note on the predictive validity of “the hyperkinetic syndrome”. J Child Psychol Psychiatry 20:61–72PubMedCrossRefGoogle Scholar
  212. Shaywitz BA, Klopper JH, Yager RD, Gordon JW (1976a) Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine. Nature 261:153–155PubMedCrossRefGoogle Scholar
  213. Shaywitz BA, Yager RD, Klopper JH (1976b) Selective brain dopamine depletion in developing rats: an experimental model of minimal brain dysfunction. Science 191:305–308PubMedCrossRefGoogle Scholar
  214. Shen RY, Choong KC (2006) Different adaptations in ventral tegmental area dopamine neurons in control and ethanol exposed rats after methylphenidate treatment. Biol Psychiatry 59:635–642PubMedCrossRefGoogle Scholar
  215. Siesser WB, Zhao J, Miller LR, Cheng SY, McDonald MP (2006) Transgenic mice expressing a human mutant beta1 thyroid receptor are hyperactive, impulsive, and inattentive. Genes Brain Behav 5:282–297PubMedCrossRefGoogle Scholar
  216. Silbergeld EK, Goldberg AM (1974) Lead-induced behavioral dysfunction: an animal model of hyperactivity. Exp Neurol 42:146–157PubMedCrossRefGoogle Scholar
  217. Silbergeld EK, Goldberg AM (1975) Pharmacological and neurochemical investigations of lead-induced hyperactivity. Neuropharmacology 14:431–444PubMedCrossRefGoogle Scholar
  218. Sleator EK, Ullmann RK (1981) Can the physician diagnose hyperactivity in the office? Pediatrics 67:13–17PubMedGoogle Scholar
  219. Smirk FH, Hall WH (1958) Inherited hypertension in rats. Nature 182:727–728PubMedCrossRefGoogle Scholar
  220. Smith A, Taylor E, Rogers JW, Newman S, Rubia K (2002) Evidence for a pure time perception deficit in children with ADHD. J Child Psychol Psychiatry 43:529–542PubMedCrossRefGoogle Scholar
  221. Sobanski E (2006) Psychiatric comorbidity in adults with attention-deficit/hyperactivity disorder (ADHD). Eur Arch Psychiatry Clin Neurosci 256(Suppl 1):i26–i31PubMedCrossRefGoogle Scholar
  222. Solanto MV (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 94:127–152PubMedCrossRefGoogle Scholar
  223. Solanto MV (2000) Clinical psychopharmacology of AD/HD: implications for animal models. Neurosci Biobehav Rev 24:27–30PubMedCrossRefGoogle Scholar
  224. Solanto MV, Abikoff H, Sonuga-Barke E, Schachar R, Logan GD, Wigal T, Hechtman L, Hinshaw S, Turkel E (2001) The ecological validity of delay aversion and response inhibition as measures of impulsivity in AD/HD: a supplement to the NIMH multimodal treatment study of AD/HD. J Abnorm Child Psychol 29:215–228PubMedCrossRefGoogle Scholar
  225. Sonuga-Barke EJ (2002) Psychological heterogeneity in AD/HD–a dual pathway model of behaviour and cognition. Behav Brain Res 130:29–36PubMedCrossRefGoogle Scholar
  226. Sonuga-Barke EJ (2005) Causal models of attention-deficit/hyperactivity disorder: from common simple deficits to multiple developmental pathways. Biol Psychiatry 57:1231–1238PubMedCrossRefGoogle Scholar
  227. Sonuga-Barke EJ, Dalen L, Remington B (2003) Do executive deficits and delay aversion make independent contributions to preschool attention-deficit/hyperactivity disorder symptoms? J Am Acad Child Adolesc Psychiatry 42:1335–1342PubMedCrossRefGoogle Scholar
  228. Speiser Z, Shved A, Gitter S (1983) Effect of propranolol treatment in pregnant rats on motor activity and avoidance learning of the offspring. Psychopharmacology (Berl) 79:148–154CrossRefGoogle Scholar
  229. Spencer TJ (2006) ADHD and comorbidity in childhood. J Clin Psychiatry 67(suppl 8):27–31PubMedGoogle Scholar
  230. Sprich-Buckminster S, Biederman J, Milberger S, Faraone SV, Lehman BK (1993) Are perinatal complications relevant to the manifestation of ADD? Issues of comorbidity and familiality. J Am Acad Child Adolesc Psychiatry 32:1032–1037PubMedCrossRefGoogle Scholar
  231. Stocker SD, Muldoon MF, Sved AF (2003) Blunted fenfluramine-evoked prolactin secretion in hypertensive rats. Hypertension 42:719–724PubMedCrossRefGoogle Scholar
  232. Streissguth AP, Sampson PD, Olson HC, Bookstein FL, Barr HM, Scott M, Feldman J, Mirsky AF (1994) Maternal drinking during pregnancy: attention and short-term memory in 14-year-old offspring – a longitudinal prospective study. Alcohol Clin Exp Res 18:202–218PubMedCrossRefGoogle Scholar
  233. Sutherland KR, Alsop B, McNaughton N, Hyland BI, Tripp G, Wickens JR (2009) Sensitivity to delay of reinforcement in two animal models of attention deficit hyperactivity disorder (ADHD). Behav Brain Res 205:372–376PubMedCrossRefGoogle Scholar
  234. Thanos PK, Ivanov I, Robinson JK, Michaelides M, Wang GJ, Swanson JM, Newcorn JH, Volkow ND (2010) Dissociation between spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats in baseline performance and methylphenidate response on measures of attention, impulsivity and hyperactivity in a visual stimulus position discrimination task. Pharmacol Biochem Behav 94:374–379Google Scholar
  235. Thompson CC, Potter GB (2000) Thyroid hormone action in neural development. Cereb Cortex 10:939–945PubMedCrossRefGoogle Scholar
  236. Todd RD, Sitdhiraksa N, Reich W, Ji TH, Joyner CA, Heath AC, Neuman RJ (2002) Discrimination of DSM-IV and latent class attention-deficit/hyperactivity disorder subtypes by educational and cognitive performance in a population-based sample of child and adolescent twins. J Am Acad Child Adolesc Psychiatry 41:820–828PubMedCrossRefGoogle Scholar
  237. Todd RD, Lobos EA, Sun LW, Neuman RJ (2003) Mutational analysis of the nicotinic acetylcholine receptor alpha 4 subunit gene in attention deficit/hyperactivity disorder: evidence for association of an intronic polymorphism with attention problems. Mol Psychiatry 8:103–108PubMedCrossRefGoogle Scholar
  238. Trommer BL, Hoeppner JA, Lorber R, Armstrong KJ (1988) The go-no-go paradigm in attention deficit disorder. Ann Neurol 24:610–614PubMedCrossRefGoogle Scholar
  239. Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003a) Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl) 165:260–269Google Scholar
  240. Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003b) Relative lack of cognitive effects of methylphenidate in elderly male volunteers. Psychopharmacology (Berl) 168:455–464CrossRefGoogle Scholar
  241. Vaidya CJ, Austin G, Kirkorian G, Ridlehuber HW, Desmond JE, Glover GH, Gabrieli JD (1998) Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proc Natl Acad Sci USA 95:14494–14499PubMedCrossRefGoogle Scholar
  242. Valera EM, Faraone SV, Murray KE, Seidman LJ (2007) Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 61:1361–1369PubMedCrossRefGoogle Scholar
  243. van den Bergh FS, Bloemarts E, Chan JS, Groenink L, Olivier B, Oosting RS (2006) Spontaneously hypertensive rats do not predict symptoms of attention-deficit hyperactivity disorder. Pharmacol Biochem Behav 83:380–390PubMedCrossRefGoogle Scholar
  244. van Gaalen MM, Brueggeman RJ, Bronius PF, Schoffelmeer AN, Vanderschuren LJ (2006) Behavioral disinhibition requires dopamine receptor activation. Psychopharmacology (Berl) 187:73–85CrossRefGoogle Scholar
  245. Viggiano D, Vallone D, Welzl H, Sadile AG (2002) The Naples High- and Low-Excitability rats: selective breeding, behavioral profile, morphometry, and molecular biology of the mesocortical dopamine system. Behav Genet 32:315–333PubMedCrossRefGoogle Scholar
  246. Wallis D, Russell HF, Muenke M (2008) Review: Genetics of attention deficit/hyperactivity disorder. J Pediatr Psychol 33:1085–1099PubMedCrossRefGoogle Scholar
  247. Watanabe Y, Fujita M, Ito Y, Okada T, Kusuoka H, Nishimura T (1997) Brain dopamine transporter in spontaneously hypertensive rats. J Nucl Med 38:470–474PubMedGoogle Scholar
  248. Whalen CK, Henker B (1976) Psychostimulants and children: a review and analysis. Psychol Bull 83:1113–1130PubMedCrossRefGoogle Scholar
  249. Wilens TE, Vitulano M, Upadhyaya H, Adamson J, Sawtelle R, Utzinger L, Biederman J (2008) Cigarette smoking associated with attention deficit hyperactivity disorder. J Pediatr 153(3):414–419PubMedCrossRefGoogle Scholar
  250. Wilkinson RT (1963) Interaction of noise with knowledge of results and sleep deprivation. J Exp Psychol 66:332–337PubMedCrossRefGoogle Scholar
  251. Willner P (1986) Validation criteria for animal models of human mental disorders: learned helplessness as a paradigm case. Prog Neuropsychopharmacol Biol Psychiatry 10:677–690PubMedCrossRefGoogle Scholar
  252. Wilson MC (2000) Coloboma mouse mutant as an animal model of hyperkinesis and attention deficit hyperactivity disorder. Neurosci Biobehav Rev 24:51–57PubMedCrossRefGoogle Scholar
  253. Winstanley CA, Theobald DE, Cardinal RN, Robbins TW (2004) Contrasting roles of basolateral amygdala and orbitofrontal cortex in impulsive choice. J Neurosci 24:4718–4722PubMedCrossRefGoogle Scholar
  254. Winstanley CA, Eagle DM, Robbins TW (2006) Behavioral models of impulsivity in relation to ADHD: translation between clinical and preclinical studies. Clin Psychol Rev 26:379–395PubMedCrossRefGoogle Scholar
  255. Wultz B, Sagvolden T, Moser EI, Moser MB (1990) The spontaneously hypertensive rat as an animal model of attention-deficit hyperactivity disorder: effects of methylphenidate on exploratory behavior. Behav Neural Biol 53:88–102PubMedCrossRefGoogle Scholar
  256. Wyss JM, Fisk G, van Groen T (1992) Impaired learning and memory in mature spontaneously hypertensive rats. Brain Res 592:135–140PubMedCrossRefGoogle Scholar
  257. Xu C, Shen RY (2001) Amphetamine normalizes the electrical activity of dopamine neurons in the ventral tegmental area following prenatal ethanol exposure. J Pharmacol Exp Ther 297:746–752PubMedGoogle Scholar
  258. Zelazo PD, Mueller U (2002) Executive function in typical and atypical development. In: Goswami U (ed) Handbook of childhood cognitive development. Blackwell, London, pp 445–469CrossRefGoogle Scholar
  259. Zhang K, Tarazi FI, Baldessarini RJ (2001) Role of dopamine D(4) receptors in motor hyperactivity induced by neonatal 6-hydroxydopamine lesions in rats. Neuropsychopharmacology 25:624–632PubMedCrossRefGoogle Scholar
  260. Zhang K, Davids E, Tarazi FI, Baldessarini RJ (2002) Effects of dopamine D4 receptor-selective antagonists on motor hyperactivity in rats with neonatal 6-hydroxydopamine lesions. Psychopharmacology (Berl) 161:100–106CrossRefGoogle Scholar
  261. Zimering RT, Burright RG, Donovick PJ (1982) Effects of pre-natal and continued lead exposure on activity levels in the mouse. Neurobehav Toxicol Teratol 4:9–14PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Experimental Psychology, Behavioural and Clinical Neuroscience InstituteUniversity of CambridgeCambridgeUK

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