Skip to main content
SpringerLink
Log in

Dopamine Knockouts and Behavior

  • Chapter
Attention Deficit Hyperactivity Disorder

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

  • 2101 Accesses

Abstract

The expression of behavior is regulated by complex cortical neural networks. These interact with several telencephalic structures, such as the basal ganglia, amygdala complex, and hippocampal cortex. All these systems are modulated by subcortical influences (see ref. 1), represented by cholinergic neurons of Meynert’s basal nucleus, dopamine (DA) neurons in the ventral tegmental area (VTA), serotonergic neurons in the raphe nuclei, norepinephrine neurons in the locus coeruleus, and histamine neurons in the posterior hypothalamus.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Robbins TW, Everitt BJ. Motivation and reward. In: Zigmond MJ, Bloom FE, Landis SC, Roberts JL, Squire LR, eds. Fundamental neuroscience. New York: Academic Press, 1999;1245–1277.

    Google Scholar 

  2. Robbins TW. Arousal systems and attentional processes. Biol Psychol 1997;45:57–71.

    Article  PubMed  CAS  Google Scholar 

  3. Wise RA, Hoffman DC. Localization of drug reward mechanisms by intracranial injections. Synapse 1992;10:247–263.

    Article  PubMed  CAS  Google Scholar 

  4. Wise RA. Neurobiology of addiction. Curr Opin Neurobiol 1996;6:243–251.

    Article  PubMed  CAS  Google Scholar 

  5. Wise RA. Brain reward circuitry: insights from unsensed incentives. Neuron 2002;36:229–240.

    Article  PubMed  CAS  Google Scholar 

  6. Fibiger HC, Phillips AG. Reward, motivation, cognition, psychobiology of mesotelencephalic dopamine systems. In: Bloom FE, ed. Handbook of physiology-the nervous system IV. Baltimore, MD, Williams and Wilkins, 1986.

    Google Scholar 

  7. Canavan AGM, Passingham RE, Marsden CD, Quinn N, Wyke M, Polkey CE. The performance on learning tasks of patients in the early stages of Parkinson’s disease. Neuropsychol 27:141–156.

    Google Scholar 

  8. Robinson TE, Berridge KC. The neural basis for drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 1993;18:247–291.

    Article  PubMed  CAS  Google Scholar 

  9. Knowlton BJ, Mangels JA, Squire LR. A neostriatal habit learning system in humans. Science 1996;273:1399–1402.

    Article  PubMed  CAS  Google Scholar 

  10. Robbins TW, Everitt BJ. Neurobehavioural mechanisms of reward and motivation. Curr Opin Neurobiol 1996;6:228–236.

    Article  PubMed  CAS  Google Scholar 

  11. Andeìn NE, Fuxe K, Hamberger B, Hokfelt T. A quantitative study on the nigro-neostriatal dopamine neurons. Acta Physiol Scand 1966;67:306–312.

    Article  CAS  Google Scholar 

  12. Kalivas PW, Nakamura M. Neural systems for behavioral activation and reward. Curr Opin Neurobiol 1999;9:223–237.

    Article  PubMed  CAS  Google Scholar 

  13. Dahlstrom A, Fuxe K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in cell bodies of brain stem neurons. Acta Physiol Scand 1964;62,Suppl. 232:1–55.

    Google Scholar 

  14. Freund TF, Powell JF, Smith AD. Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines. Neuroscience 1984;13:1189–1215.

    Article  PubMed  CAS  Google Scholar 

  15. Deutch AY, Bourdelais AJ, Zahm DS. The nucleus accumbens core and shell: accumbal compartments and their functional attributes. In: Kalivas PW, Barnes CD, eds. Limbic circuits and neuropsychiatry. CRC Press, London: 1993:45–88.

    Google Scholar 

  16. Bouyer JJ, Park DH, Joh TH, Pickel VM. Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum. Brain Res 1984;302:267–275.

    Article  PubMed  CAS  Google Scholar 

  17. Carlezon WA, Jr., Wise RA. Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens shell potentiate medial forebrain bundle brain stimulation reward. Psychopharmacology (Berl) 1996;128:413–420.

    Article  CAS  Google Scholar 

  18. Zahm DS. An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neurosci Biobehav Rev 2000;24:85–105.

    Article  PubMed  CAS  Google Scholar 

  19. Sellings LH, Clark PB. Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core. J Neurosci 2003;23:6295–6303.

    PubMed  CAS  Google Scholar 

  20. Routtenberg A. Intracranial chemical injection and behavior: A critical review. Behav Biol 1972;7:601–641.

    Article  PubMed  CAS  Google Scholar 

  21. Corbett D, Silva LR, Stellar JR. An investigation of the factors affecting development of frontal cortex self-stimulation. Physiol Behav 1985;34:89–95.

    Article  PubMed  CAS  Google Scholar 

  22. You Z-B, Tzschentke TM, Brodin E, Wise RA. Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: an in vivo microdialysis study in freely moving rats. J Neurosci 1998;18:6492–6500.

    PubMed  CAS  Google Scholar 

  23. Hoebel BG, Monaco AP, Hernandez L, Aulisi EF, Stanley BG, Lenard L. Self-injection of amphetamine directly into the brain. Psychopharmacology (Berl) 1983;81:158–163.

    Article  CAS  Google Scholar 

  24. Carr GD, White NM. Conditioned place preference from intra-accumbens but not intra-caudate amphetamine injections. Life Sci 1983;33:2551–2557.

    Article  PubMed  CAS  Google Scholar 

  25. Carlezon WA, Jr., Devine DP, Wise RA. Habit-forming actions of nomifensine in nucleus accumbens. Psychopharmacology (Berl) 1995;122:194–197.

    Article  CAS  Google Scholar 

  26. Fallon JH, Loughlin SE. Monoamine innervation of the forebrain: collateralization. Brain Res Bull 1982;9:295–307.

    Article  PubMed  CAS  Google Scholar 

  27. Bozarth MA, Wise RA. Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci 1981;28:551–555.

    Article  PubMed  CAS  Google Scholar 

  28. Welzl H, Kuhn G, Huston JP. Self-administration of small amounts of morphine through glass micropipettes into the ventral tegmental area of the rat. Neuropharmacology 1989;28:1017–1023.

    Article  PubMed  CAS  Google Scholar 

  29. Devine DP, Wise RA. Self-administration of morphine, dopamine MGO, and DPDPE into the ventral tegmental area of rats. J Neurosci 1994;14:1978–1984.

    PubMed  CAS  Google Scholar 

  30. David V, Durkin TP, Cazala P. Differential effects of the dopamine D2/D3 receptor antagonist sulpiride on self-administration of morphine into the ventral tegmental area or the nucleus accumbens. Psychopharmacology (Berl) 2002;160:307–317.

    Article  CAS  Google Scholar 

  31. Johnson SW, North RA. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 1992;12:483–488.

    PubMed  CAS  Google Scholar 

  32. Hynes M, Rosenthal A. Specification of dopaminergic and serotonergic neurons in the vertebrate CNS. Curr Opin Neurobiol 1999;9:26–36.

    Article  PubMed  CAS  Google Scholar 

  33. Ye W, Shimamura K, Rubenstein JL, Hynes MA, Rosenthal A. FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 1998;93:755–766.

    Article  PubMed  CAS  Google Scholar 

  34. Shamim H, Mahmood R, Logan C, Doherty P, Lumsden A, Mason I. Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain. Development 1999;126:945–959.

    PubMed  CAS  Google Scholar 

  35. DiPorzio U, Pernas-Alonso R, Perrone-Capano C. Development of dopaminergic neurons. Austin, TX: Landes company, 1999.

    Google Scholar 

  36. Danielian PS, McMahon AP. Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development. Nature 1996;383:332–334.

    Article  PubMed  CAS  Google Scholar 

  37. Wurst W, Auerbach ABJAL. Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 1994;120:2065–2075.

    PubMed  CAS  Google Scholar 

  38. Hanks M, Wurst W, Anson-Cartwright L, Auerbach AB, Joyner AL. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. Science 1995;269:679–682.

    Article  PubMed  CAS  Google Scholar 

  39. Favor J. The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney. Proc Natl Acad Sci USA 1996;93:13,870–875.

    Article  PubMed  CAS  Google Scholar 

  40. Urbanek P, Fetka I, Meisler MH, Busslinger M. Cooperation of Pax2 and Pax5 in midbrain and cerebellum development. Proc Natl Acad Sci USA 1997;94:5703–5708.

    Article  PubMed  CAS  Google Scholar 

  41. Hynes M. Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 1995;15:35–44.

    Article  PubMed  CAS  Google Scholar 

  42. Smidt M. A novel homeodomain gene Ptx3 has higly restricted brain expression in mesencephalic dopaminergic neurons. Proc Natl Acad Sci USA 1997;94:13,305–13,310.

    Article  PubMed  CAS  Google Scholar 

  43. Zetterstrom RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T. Dopamine neuron agenesis in Nurr1-deficient mice. Science 1997;276:248–250.

    Article  PubMed  CAS  Google Scholar 

  44. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, et al. Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA 1998;95:4013–4018.

    Article  PubMed  CAS  Google Scholar 

  45. Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP. A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci 2000;3:337–341.

    Article  PubMed  CAS  Google Scholar 

  46. Yue Y, Widmer DA, Halladay AK, Cerretti DP, Wagner GC, Dreyer JL, Zhou R. Specification of distinct dopaminergic neural pathways: roles of the Eph family receptor EphB1 and ligand ephrin-B2. J Neurosci 1999;19:2090–2101.

    PubMed  CAS  Google Scholar 

  47. Kobayashi K, Morita S, Sawada H, et al. Targeted disruption of the tyrosine hydroxylase locus results in severe catecholamine depletion and perinatal lethality in mice. J Biol Chem 1995;270:27,235–27,243.

    Article  PubMed  CAS  Google Scholar 

  48. Zhou QY, Palmiter RD. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 1995;83:1197–1209.

    Article  PubMed  CAS  Google Scholar 

  49. Zhou QY, Quaife CJ, Palmiter RD. Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development. Nature 1995;374:640–643.

    Article  PubMed  CAS  Google Scholar 

  50. Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG. Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc Natl Acad Sci USA 1998;95:4029–4034.

    Article  PubMed  CAS  Google Scholar 

  51. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 1996;379:606–612.

    Article  PubMed  CAS  Google Scholar 

  52. Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke EJS, Jensen PS, Cantwell DP. Attention deficit hyperactivity disorder and hyperkinetic disorder. Lancet 1998;351:329–343.

    Article  Google Scholar 

  53. Cook EH, Jr., Stein MA, Krasowski MD, et al. Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 1995;56:993–998.

    PubMed  CAS  Google Scholar 

  54. Gill M, Daly G, Heron S, Hawi Z, Fitzgerald M. Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol Psychiatry 1997;2:311–331.

    Article  PubMed  CAS  Google Scholar 

  55. Waldman ID, Rowe DC, Abramowitz A, et al. Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity. Am J Hum Genet 1998;63:1767–1776.

    Article  PubMed  CAS  Google Scholar 

  56. Gainetdinov R, Wetsel W, Jones S, Levin E, Jaber M, Caron M. Role of serotonine in the paradoxical calming effect of psychostimulants on hyperactivity. Science 1999;283:397–401.

    Article  PubMed  CAS  Google Scholar 

  57. Bosse R, Fumagalli F, Jaber M, et al. Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter. Neuron 1997;19:127–138.

    Article  PubMed  CAS  Google Scholar 

  58. Zhuang X, Oosting RS, Jones RS, et al. Hyperactivity and impaired response habituation in hyperdopaminergic mice. PNAS 2001;98:1982–1987.

    Article  PubMed  CAS  Google Scholar 

  59. Crabbe JC. Genetic differences in locomotor activation in mice. Pharmacol Biochem Behav 1986;25:289–292.

    Article  PubMed  CAS  Google Scholar 

  60. Laviola G, Renna G, Bignami G, Cuomo V. Ontogenetic and pharmacological dissociation of various components of locomotor activity and habituation in the rat. Int J Dev Neurosci 1988;6:431–438.

    Article  PubMed  CAS  Google Scholar 

  61. Pecina S, Cagniard B, Berridge KC, Aldrige JW, Zhuang X. Hyperdopaminergic mutant mice have higher “wanting” but not “liking” for sweet rewards. J Neurosci 2003;23:9395–9402.

    PubMed  CAS  Google Scholar 

  62. Gimenez-Llort L, Martinez E, Ferre S. Different effects of dopamine antagonists on spontaneous and NMDA-induced motor activity in mice. Pharmacol Biochem Behav 1997;56:549–553.

    Article  PubMed  CAS  Google Scholar 

  63. Gerlai R, McNamara A, Choi-Lundberg DL, et al. Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation. Eur J Neurosci 2001;14:1153–1163.

    Article  PubMed  CAS  Google Scholar 

  64. Nestler EJ. Molecular neurobiology of drug addiction. Neuropsychopharmacology 1994;11:77–87.

    PubMed  CAS  Google Scholar 

  65. Castellanos FX, Tannock R. Neuroscience of Attention-Deficit/Hyperactivity Disorder: the search for endophenotypes. Nature Reviews 2002;3:617–628.

    PubMed  CAS  Google Scholar 

  66. Castellanos FX, Giedd JN, Eckburg P, et al. Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder. Am J Psychiatry 1994;151:1791–1796.

    PubMed  CAS  Google Scholar 

  67. Castellanos FX, Giedd JN, Marsh WL, et al. Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry 1996;53:607–616.

    PubMed  CAS  Google Scholar 

  68. Jackson DM, Westlind-Danielsson A. Dopamine receptors: molecular biology, biochemistry and behavioural aspects. Pharmacol Ther 1994;64:291–370.

    Article  PubMed  CAS  Google Scholar 

  69. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiol Rev 1998;78:189–225.

    PubMed  CAS  Google Scholar 

  70. Neve KA, Neve RL. The dopamine receptors. Totowa NJ, Humana Press, 1997.

    Google Scholar 

  71. Gerfen CR. The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 1992;15:133–139.

    Article  PubMed  CAS  Google Scholar 

  72. Aizman O, Brismar H, Uhlen P, et al. Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons. Nat Neurosci 2000;3:226–230.

    Article  PubMed  CAS  Google Scholar 

  73. Ikemoto S, Glazier BS, Murphy JM, McBride WJ. Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward. J Neurosci 1997;17:8580–8587.

    PubMed  CAS  Google Scholar 

  74. Sibley DR. New insights into dopamine rgic receptor function using antisense and genetically altered animals. Annu Rev Pharmacol Toxicol 1999;39:313–341.

    Article  PubMed  CAS  Google Scholar 

  75. Glickstein SB, Schmauss C. Dopamine receptor function: lessons from knockout mice. Pharmacol Ther 2001;91:63–83.

    Article  PubMed  CAS  Google Scholar 

  76. Ariano MA, Wang J, Noblett KL, Larson ER, Sibley D. Cellular distribution of the rat D4 dopamine receptor protein in the CNS using anti-receptor antisera. Brain Res 1997;752:26–34.

    Article  PubMed  CAS  Google Scholar 

  77. Ciliax DJ, Nash N, Heilman C, et al. Dopamine D5 receptor immunolocalization in rat and monkey brain. Synapse 2000;37:125–145.

    Article  PubMed  CAS  Google Scholar 

  78. Weiner DM, Levey AI, Sunahara RK, et al D1 and D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci USA 1991;88:1859–1863.

    Article  PubMed  CAS  Google Scholar 

  79. di Porzio U, Pernas-Alonso R, Perrone-Capano C. Development of dopaminergic neurons. Landes, Austin, TX, 1999:1.

    Google Scholar 

  80. Blandini F, Fancellu R, Orzi F, et al Selective stimulation of striatal dopamine receptors of the D1-or D2-class causes opposite changes of fos expression in the rat cerebral cortex. Eur J Neurosci 2003;17:763–770.

    Article  PubMed  Google Scholar 

  81. Drago J, Padungchichot P, Accili D, Fuchs S. Dopamine receptors and dopamine transporter in brain function and addictive behaviors: insight from targeted mouse mutants. Dev Neurosci 1998;20:188–203.

    Article  PubMed  CAS  Google Scholar 

  82. Xu M, Hu XT, Cooper DC, et al Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine D1 receptor mutant mice [see comments]. Cell 1994;79:945–955.

    Article  PubMed  CAS  Google Scholar 

  83. Xu M, Moratalla R, Gold LH, et al Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell 1994;79:729–742.

    Article  PubMed  CAS  Google Scholar 

  84. Drago J, Gerfen CR, Lachowicz JE, et al Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci USA 1994;91:12,564–568.

    Article  PubMed  CAS  Google Scholar 

  85. Drago J, Gerfen CR, Westphal H, Steiner H. D1 dopamine receptor-deficient mouse: cocaine-induced regulation of immediate-early gene and substance P expression in the striatum. Neuroscience 1996;74:813–823.

    Article  PubMed  CAS  Google Scholar 

  86. McNamara FN, Clifford JJ, Tighe O, et al. Congenic D1A dopamine receptor mutants: ethologically based resolution of behavioural topography indicates genetic background as a determinant of knockout phenotype. Neuropsychopharmacology 2003;28:86–99.

    Article  PubMed  CAS  Google Scholar 

  87. Viggiano D, Vallone D, Ruocco LA, Sadile AG. Behavioral pharmacological, morpho-functional molecular studies reveal a hyperfunctioning mesocortical dopamine system in an animal model of attention deficit and hyperactivity disorder. Neurosci Biobehav Rev 2003;27:683–689.

    Article  PubMed  CAS  Google Scholar 

  88. Jackson DJ, Westlind-Danielsson A. Dopamine receptors: Molecular biology, biochemistry and behavioural aspects. Pharmacol Ther 1994;64:291–369.

    Article  PubMed  CAS  Google Scholar 

  89. Baik JH, Picetti R, Saiardi A, et al Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors. Nature 1995;377:424–428.

    Article  PubMed  CAS  Google Scholar 

  90. Kelly MA, Rubinstein M, Phillips TJ, et al Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations. J Neurosci 1998;18:3470–3479.

    PubMed  CAS  Google Scholar 

  91. Jung MY, Skryabin BV, Arai M, et al Potentiation of the D2 mutant motor phenotype in mice lacking dopamine D2 and D3 receptors. Neuroscience 1999;91:911–924.

    Article  PubMed  CAS  Google Scholar 

  92. Maldonado R, Saiardi A, Valverde O, Samad TA, Roques BP, Borrelli E. Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature 1997;388:586–589.

    Article  PubMed  CAS  Google Scholar 

  93. Saiardi A, Bozzi Y, Baik JH, Borrelli E. Antiproliferative role of dopamine: loss of D2 receptors causes hormonal dysfunction and pituitary hyperplasia. Neuron 1997;19:115–126.

    Article  PubMed  CAS  Google Scholar 

  94. Kelly MA, Rubinstein M, Asa SL, et al Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice. Neuron 1997;19:103–113.

    Article  PubMed  CAS  Google Scholar 

  95. L’hirondel M, Cheramy A, Godeheu G, et al. Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice. Brain Res 1998;792:253–262.

    Article  CAS  Google Scholar 

  96. Mercuri NB, Saiardi A, Bonci A, et al Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice. Neuroscience 1997;79:323–327.

    Article  PubMed  CAS  Google Scholar 

  97. Koeltzow TE, Xu M, Cooper DC, et al Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J Neurosci 1998;18:2231–2238.

    PubMed  CAS  Google Scholar 

  98. Mansour A, Meador-Woodruff JH, Bunzow JR, Civelli O, Akil H, Watson SJ. Localization of dopamine D2 receptor mRNA and D1 and D2 receptor binding in the rat brain and pituitary: an in situ hybridization-receptor autoradiographic analysis. J Neurosci 1990;10:2587–2600.

    PubMed  CAS  Google Scholar 

  99. Usiello A, Baik JH, Rouge-Pont F, et al Distinct functions of the two isoforms of dopamine D2 receptors. Nature 2000;408:199–203.

    Article  PubMed  CAS  Google Scholar 

  100. Rouge-Pont F, Usiello A, Benoit-Marand M, Gonon F, Piazza PV, Borrelli E. Changes in extracellular dopamine induced by morphine and cocaine: crucial control by D2 receptors. J Neurosci 2002;22:3293–3301.

    PubMed  CAS  Google Scholar 

  101. Grace AA, Bunney BS, Moore H, Todd CL. Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. Trends Neurosci 1997;20:31–37.

    Article  PubMed  CAS  Google Scholar 

  102. Doppler W. Regulation of gene expression by prolactin. Rev Physiol Biochem Pharmacol 1994;124:93–130.

    Article  PubMed  CAS  Google Scholar 

  103. Picetti R, Saiardi A, Samad TA, Bozzi Y, Baik J-H, Borrelli E. Dopamine D2 receptors in signal transduction and behavior. Crit Rev Neurobiol 1997;11:121–142.

    PubMed  CAS  Google Scholar 

  104. Di Chiara G. The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 1995;38:95–137.

    Article  PubMed  Google Scholar 

  105. Dal Toso R, Sommer B, Ewert M, et al The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J 1989;8:4025–134.

    Google Scholar 

  106. Kahn RA, Weinberger J, Panah M. How selective is 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase? Response. Anesth Analg 1998;86:679–680.

    Article  Google Scholar 

  107. Weiger TM, Holmqvist MH, Levitan IB, et al A novel nervous system beta subunit that down-regulates human large conductance calcium-dependent potassium channels. J Neurosci 2000;20:3563–3570.

    PubMed  CAS  Google Scholar 

  108. Montmayeur J-P, Borrelli E. Transcription mediated by a cAMP-responsive promoter element is reduced upon activation of dopamine D2 receptors. Proc Natl Acad Sci USA 1991;88:3135–3139.

    Article  PubMed  CAS  Google Scholar 

  109. Gerfen CR. The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 1992;15:133–149.

    Article  PubMed  CAS  Google Scholar 

  110. Vallone D, Pignatelli M, Grammatikopoulus G, et al Activity, non-selective attention and emotionally in dopamine D-2/D-3 receptor knock out mice. Behav Brain Res 2002;130:141–148.

    Article  PubMed  CAS  Google Scholar 

  111. Clifford JJ, Usiello A, Vallone D, Kinsella A, Borrelli E, Waddington JL. Topographical evaluation of behavioural phenotype in a line of mice with targeted gene deletion of the D2 dopamine receptor. Neuropharmacology 2000;39:382–390.

    Article  PubMed  CAS  Google Scholar 

  112. Wang Y, Xu R, SasaokaT, Tonegawa S, Kung M-P, Sankoorikal E-B. Dopamine D2 long receptor-deficient mice display alterations in striatum-dependent functions. J Neurosci 2000;20:8305–8314.

    PubMed  CAS  Google Scholar 

  113. Fetsko LA, Xu R, Wang Y. Alterations in D1/D2 synergism may account for enhanced stereotypy and reduced climbing in mice lacking dopamine D2L receptor. Brain Res 2003;967:191–200.

    Article  PubMed  CAS  Google Scholar 

  114. Parish CL, Finkelstein DI, Drago J, Borrelli E, Horne MK. The role of dopamine receptors in regulating the size of axonal arbors. J Neurosci 2001;21:5147–157.

    PubMed  CAS  Google Scholar 

  115. Bouthenet ML, Souil E, Martres MP, Sokoloff P, Giros B, Schwartz JC. Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res 1991;564:203–219.

    Article  PubMed  CAS  Google Scholar 

  116. Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 1990;347:146–151.

    Article  PubMed  CAS  Google Scholar 

  117. Accili D, Fishburn CS, Drago J, et al A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proc Natl Acad Sci USA 1996;93:1945–1949.

    Article  PubMed  CAS  Google Scholar 

  118. Xu M, Koeltzow TE, Santiago GT, et al Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors. Neuron 1997;19:837–848.

    Article  PubMed  CAS  Google Scholar 

  119. Cornett LE, Breckinridge SM, Koike TI. Induction of V2 receptors in renal medulla of homozygous Brattleboro rats by arginine vasopressin. Peptides 1989;10:985–991.

    Article  PubMed  CAS  Google Scholar 

  120. Narita M, Mizuo K, Mizoguchi H, et al Molecular evidence for the functional role of dopamine D3 receptor in the morphine-induced rewarding effect and hyperlocomotion. J Neurosci 2003;23:1006–1012.

    PubMed  CAS  Google Scholar 

  121. Wong JY, Clifford JJ, Massalas JS, Kinsella A, Waddington JL, Drago J. Essential conservation of D(1) mutant phenotype at the level of individual topographies of behaviour in mice lacking both D(1) and D(3) dopamine receptors. Psychopharmacology (Berl) 2003;167:167–173.

    CAS  Google Scholar 

  122. Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH. Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Genet 1996;12:81–84.

    Article  PubMed  CAS  Google Scholar 

  123. Ebstein RP, Novick O, Umansky R, et al Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nat Genet 1996;12:78–80.

    Article  PubMed  CAS  Google Scholar 

  124. Malhotra AK, Virkkunen M, Rooney W, Eggert M, Linnoila M, Goldman D. The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. Mol Psychiatry 1996;1:388–391.

    PubMed  CAS  Google Scholar 

  125. Vandenbergh DJ, Zonderman AB, Wang J, Uhl GR, Costa PT. No association between novelty-seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore Longitudinal Study of Aging participants. Mol Psychiatry 1997;2:417–419.

    Article  PubMed  CAS  Google Scholar 

  126. Kuhn K, Meyer K, Nothen MM, Gansicke M, Papassotiropoulos A, Maier W. Allelic variants of dopamine receptor D4 (D4DR) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests. Am J Med Genet 1999;88:168–172.

    Article  PubMed  CAS  Google Scholar 

  127. Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA. Dopamine D4 receptor-knockout mice exhibit reduced exploration of novel stimuli. J Neurosci 1999;19:9550–9556.

    PubMed  CAS  Google Scholar 

  128. Mrzljak L, Bergson C, Pappy M, Huff R, Levenson R, Goldman-Rakic PS. Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. Nature 1996;381:245–248.

    Article  PubMed  CAS  Google Scholar 

  129. Rubinstein M, Phillips TJ, Bunzow JR, et al Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 1997;90:991–1001.

    Article  PubMed  CAS  Google Scholar 

  130. Carter CJ. Topographical distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats. Neuropharmacology 1982;21:379–383.

    Article  PubMed  CAS  Google Scholar 

  131. Lanau F, Zenner M, Civelli O, Hartman D. Epinephrine and norepinephrine act as potent agonists at the recombinant human dopamine D4 receptor. J Neurochem 1997;68:804–812.

    Article  PubMed  CAS  Google Scholar 

  132. Westerink BHC, Santiago M, De Vries JB. The release of dopamine from nerve terminals and dendrites of nigrostriatal neurons induced by excitatory amino acids in the conscious rat. Naunyn Schmiedebergs Arch Pharmacol 1992;345:523–529.

    Article  PubMed  CAS  Google Scholar 

  133. Overton P, Clark D. Electrophysiological evidence that intrastriatally administered N-methyl-D-aspartate augments striatal dopamine tone in the rat. J Neural Transm 1992;4:1–14.

    Article  CAS  Google Scholar 

  134. Kotler M, Cohen H, Segman R, et al Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. Mol Psychiatry 1997;2:251–254.

    Article  PubMed  CAS  Google Scholar 

  135. Shields PG, Lerman C, Audrain J, et al Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 1998;7:453–458.

    PubMed  CAS  Google Scholar 

  136. de Castro PI, IA, Torres P, Saiz-Ruiz J, Fernandez-Piqueras J. Genetic association study between pathological gambling and a functional DNA polymorphism at the D4 receptor gene. Pharmacogenetics 1997;7:345–348.

    Article  Google Scholar 

  137. LaHoste GJ, Swanson JM, Wigal SB, et al Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Molec Psychiatry 1996;1:121–124.

    CAS  Google Scholar 

  138. Faraone SV, Biederman J, Weiffenbach B, et al Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder. Am J Psychiatry 1999;156:768–770.

    PubMed  CAS  Google Scholar 

  139. Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH. Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 1995;65:1157–1165.

    Article  PubMed  CAS  Google Scholar 

  140. Nothen MM, Cichon S, Hemmer S, et al Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity. Hum Mol Genet 1994;3:2207.

    Article  PubMed  CAS  Google Scholar 

  141. Sunahara RK, Guan HC, O’Dowd BF, et al Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 1991;150:614–619.

    Article  Google Scholar 

  142. Tiberi M, Caron MG. High agonist-independent activity is a distinguishing feature of the dopamine D1B receptor subtype. J Biol Chem 1994;269:27,925–931.

    PubMed  CAS  Google Scholar 

  143. Yan Z, Surmeier DJ. D5 dopamine receptors regulate Zn2+-sensitive GABAA currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Neuron 1997;19:1115–1126.

    Article  PubMed  CAS  Google Scholar 

  144. Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB. Direct protein-protein coupling enables cross-talk between dopamine D5 and-aminobutyric acid A receptors. Nature 2000;403:274–280.

    Article  PubMed  CAS  Google Scholar 

  145. Muir WJ, Thomson ML, McKeon P, et al Markers close to the dopamine D5 receptor gene (DRD5) show significant association with schizophrenia but not bipolar disorder. Am J Med Genet 2001;105:152–158.

    Article  PubMed  CAS  Google Scholar 

  146. Vanyukov MM, Moss HB, Gioio AE, Hughes HB, Kaplan BB, Tarter RE. An association between a microsatellite polymorphism at the DRD5 gene and the liability to substance abuse: pilot study. Behav Genet 1998;28:75–82.

    Article  PubMed  CAS  Google Scholar 

  147. Hollon TR, Bek MJ, Lachowicz JE, et al Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci 2002;22:10,801–811.

    PubMed  CAS  Google Scholar 

  148. Rivkees S, Lachowicz JE. Functional D1 and D5 dopamine receptors are expressed in the suprachiasmatic, supraoptic and paraventricular nuclei of primates. Synapse 1997;26:1–10.

    Article  PubMed  CAS  Google Scholar 

  149. Apostolakis EM, Gara J, Fox C, et al Dopamine rgic regulation of progesterone receptors: brain D5 dopamine receptors mediate induction of lordosis by D1-like agonists in rats. J Neurosci 1996;16:4823–4834.

    PubMed  CAS  Google Scholar 

  150. Apostolakis EM, Garai J, O’Malley BW, Clark JH. In vivo regulation of central nervous system progesterone receptors: cocaine induces steroid-dependent behavior through dopamine transporter modulation of D5 receptors in rats. Mol Endocrinol 1996;10:1595–604.

    Article  PubMed  CAS  Google Scholar 

  151. Dahmer MK, Senogles SE. Dopaminergic inhibition of catecholamine secretion from chromaffin cells: evidence that inhibition is mediated by D4 and D5 dopamine receptors. J Neurochem 1996;66:222–232.

    Article  PubMed  CAS  Google Scholar 

  152. Mezey E, Eisenhofer G, Harta G, et al A novel nonneuronal catecholaminergic system: exocrine pancreas synthesizes and releases dopamine. Proc Natl Acad Sci USA 1996;93:10,377–82.

    Article  PubMed  CAS  Google Scholar 

  153. Dziewczapolski G, Menalled LB, Garcia MC, Mora MA, Gershanik OS, Rubinstein M. Opposite roles of D1 and D5 dopamine receptors in locomotion revealed by selective antisense oligonucleotides. Neurorep 1998;9:1–5.

    Article  CAS  Google Scholar 

  154. Greengard P, Allen PB, Nairn AC. Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 1999;23:435–447.

    Article  PubMed  CAS  Google Scholar 

  155. Sadile AG. Long-term habituation of theta-related activity components of albino rats in the Làtmaze. In: Sanberg PR, Ossenkopp KP, Kavaliers M, eds. Motor activity and movement disorders: measurement and analysis. Totowa, NJ: Humana Press, 1996:1–54.

    Google Scholar 

  156. Whishaw IQ, Vanderwolf CH. Hippocampal EEG and behavior: changes in amplitude and frequency of RSA (theta rhythm) associated with spontaneous and learned movement patterns in rats and cats. Behav Biol 1973;8:461–484.

    Article  PubMed  CAS  Google Scholar 

  157. Pellicano MP, Siciliano F, Sadile AG. The dose and genotype-dependent effects of post-trial MK-801 and CPP on long-term habituation to novelty in rats reveal a modulatory role of NMdopamine receptors on behavioral plasticity. Neurosci Lett Suppl 1992;43:S86.

    Google Scholar 

  158. Van Abeelen JHF. Genetics of rearing behavior in mice. Behav Genet 1970;1:71–76.

    Article  PubMed  Google Scholar 

  159. Sanders DC. The Bethlem lines: genetic selection for high and low rearing activity in rats. Behav Genet 1981;11:491–503.

    Article  PubMed  CAS  Google Scholar 

  160. Aspide R, Fresiello A, De Filippis G, Gironi Carnevale UA, Sadile AG. Non selective attention in a rat model of hyperactivity and attention deficit: subchronic methylphenidate and nitric oxide synthesis inhibitor treatment. Neurosci Biobehav Rev 2000;24:59–71.

    Article  PubMed  CAS  Google Scholar 

  161. Aspide R, Gironi Carnevale UA, Sergeant JA, Sadile AG. Non-selective attention and nitric oxide in putative animal models of attention-deficit hyperactivity disorder. Behav Brain Res 1998;95:123–133.

    Article  PubMed  CAS  Google Scholar 

  162. Aspide R, Gironi Carnevale UA, Sagvolden T, Sergeant JA, Sadile AG. Novelty-induced rearing duration as index of attention at low motivational levels in two animal models of ADHD in children. Proc IBNS, Cancun, Mexico, 1996;5:65.

    Google Scholar 

  163. Grillner P, Mercuri N. Intrinsic membrane properties and synaptic inputs regulating the firing activity of the dopamine neurons. Behav Brain Res 2002;130:149–169.

    Article  PubMed  CAS  Google Scholar 

  164. Chiasson BJ, Armstrong JN, Hooper ML, Murphy PR, Robertson HA. The application of antisense oligonucleotide technology to the brain: Some pitfalls. Cell Mol Neurobiol 1994;14:507–522.

    Article  PubMed  CAS  Google Scholar 

  165. Landgraf R, Naruo T, Vecsernyes M, Neumann I. Neuroendocrine and behavioral effects of anti-sense oligonucleotides. Eur J Endocrinol 1997;137:326–335.

    Article  PubMed  CAS  Google Scholar 

  166. Menalled LB, Dziewczapolski G, Garcia MC, Rubinstein M, Gershanik OS. D3 receptor knockdown through antisense oligonucleotide administration supports its inhibitory role in locomotion. Neurorep 1999;10:3131–3136.

    Article  CAS  Google Scholar 

  167. Sadile AG, ed. Modeling ADHD in rodent mutants. Neurosci Biobehav Rev 2000;24:1–169.

    Google Scholar 

  168. Sagvolden T. Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit hyperactivity disorder (AD/HD). Neurosci Biobehav Rev 2000;24:31–40.

    Article  PubMed  CAS  Google Scholar 

  169. Moisan M, Courvoisier H, Bihoreau M, et al A major quantitative trait locus influences hyperactivity in the WKHA rat. Nature Genet 1996;14:471–473.

    Article  PubMed  CAS  Google Scholar 

  170. Cerbone A, Pellicano MP, Sadile AG. Evidence for and against the Naples high-and low-excitability rats as genetic model to study hippocampal functions. Neurosci Biobehav Rev 1993;17:295–304.

    Article  PubMed  CAS  Google Scholar 

  171. Solanto MV. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 1998;94:127–152.

    Article  PubMed  CAS  Google Scholar 

  172. Russell VA. The nucleus accumbens motor-limbic interface of the spontaneously hypertensive rat as studied in-vitro by the superfusion slice technique. Neurosci Biobehav Rev 2000;24:133–136.

    Article  PubMed  CAS  Google Scholar 

  173. Sadile AG. Multiple evidence of a segmental defect in the anterior forebrain of an animal model of hyperactivity and attention deficit. Neurosci Biobehav Rev 2000;24:161–169.

    Article  PubMed  CAS  Google Scholar 

  174. Viggiano D, Vallone D, Sadile A. Dysfunctions of the dopamine systems and ADHD: evidence from animals and modeling. Neural Plast 2004;11:97–114.

    Article  PubMed  CAS  Google Scholar 

  175. Beltramo M, Rodriguez de Fonseca FR, Navarro M, et al Reversal of dopamine D2-receptor responses by an anandamide trasport inhibitor. J Neurosci 2000;20:3401–3407.

    PubMed  CAS  Google Scholar 

  176. Viggiano D, Ruocco LA, Pignatelli M, Grammatikopoulos G, Sadile AG. Prenatal elevation of endocannabinoids corrects the unbalance between dopamine systems and reduces activity in the Naples high excitability rats. Neurosci Biobehav Rev 2003;27:129–139.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Second University of Naples, Naples, Italy

    Davide Viggiano MD, PhD, Daniela Vallone MD, Lucia A. Ruocco DR & Adolfo G. Sadile MD

Authors
  1. Davide Viggiano MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Vallone MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucia A. Ruocco DR
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adolfo G. Sadile MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Kosair Children’s Hospital, Research Institute, Departments of Pediatrics, Pharmacology, and Toxicology, University of Louisville, Louisville, KY

    David Gozal MD

  2. Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY

    Dennis L. Molfese PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Viggiano, D., Vallone, D., Ruocco, L.A., Sadile, A.G. (2005). Dopamine Knockouts and Behavior. In: Gozal, D., Molfese, D.L. (eds) Attention Deficit Hyperactivity Disorder. Contemporary Clinical Neuroscience. Humana Press. https://doi.org/10.1385/1-59259-891-9:055

Download citation

  • DOI: https://doi.org/10.1385/1-59259-891-9:055

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-312-1

  • Online ISBN: 978-1-59259-891-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation