Strengths and limitations of genetic models of ADHD

ADHD Attention Deficit and Hyperactivity Disorders

Volumn 2, Issue 1, 2010, Pages 21-30

  Gainetdinov, Raul R ^a  

^a ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

Author keywords

Adhd dopamine serotonin dopamine transporter animal model psychostimulants

Indexed keywords

ALPHA [AMINO(4 AMINOPHENYLTHIO)METHYLENE] 2 (TRIFLUOROMETHYL)PHENYLACETONITRILE; AMPHETAMINE; DOPAMINE; DOPAMINE TRANSPORTER; ENZYME INHIBITOR; METHYLPHENIDATE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE INHIBITOR; NORADRENALIN TRANSPORTER; PARATHYROID HORMONE RECEPTOR; PSYCHOSTIMULANT AGENT; SEROTONIN ANTAGONIST; SEROTONIN TRANSPORTER; SMALL INTERFERING RNA; THYROID HORMONE; UNCLASSIFIED DRUG;

ARTICLE; ASSOCIATION; ATTENTION DEFICIT DISORDER; COGNITIVE DEFECT; COMORBIDITY; CONSTRUCT VALIDITY; DAT1 GENE; DOPAMINE RELEASE; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; ENDOCRINE DISEASE; ENVIRONMENTAL FACTOR; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FACE VALIDITY; GENE; GENE DISRUPTION; GENE OVEREXPRESSION; GENETIC MODEL; HETEROZYGOSITY; HUMAN; HYPERACTIVITY; IMPULSIVENESS; KNOCKOUT MOUSE; NEUROMODULATION; NEUROTRANSMISSION; NEUROTRANSMITTER UPTAKE; NONHUMAN; PATHOGENESIS; PREDICTIVE VALIDITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; SERT GENE; SNAP 25 GENE; TRANSGENIC MOUSE; WILD TYPE;

ANIMALS; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; DISEASE MODELS, ANIMAL; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; ENDOPHENOTYPES; HUMANS; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; MODELS, GENETIC;

EID: 79960063946     PISSN: 18666116     EISSN: 18666647     Source Type: Journal    
DOI: 10.1007/s12402-010-0021-3     Document Type: Article

References (78)

1. Amara SG, Sonders MS (1998) Neurotransmitter transporters as molecular targets for addictive drugs. Drug Alcohol Depend 51:87-96
2. Barkley RA (1997) Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull 121:65-94
3. 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 29:221-228
4. Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG (2006) Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice. J Biol Chem 281:32072-32080
5. Bortolozzi A, Artigas F (2003) Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors. Neuropsychopharmacology 28:421-434
6. Bosse R, Fumagalli F, Jaber M, Giros B, Gainetdinov RR, Wetsel WC, Missale C, Caron MG (1997) Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter. Neuron 19:127-138
7. Brunner D, Buhot MC, Hen R, Hofer M (1999) Anxiety, motor activation, and maternal-infant interactions in 5HT1B knockout mice. Behav Neurosci 113:587-601
8. Cagniard B, Balsam PD, Brunner D, Zhuang X (2006) Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward. Neuropsychopharmacology 31:1362-1370
9. Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML (2001) Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu Rev Pharmacol Toxicol 41:237-260
10. Cook EH Jr, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, Leventhal BL (1995) Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56:993-998
11. Costa RM, Gutierrez R, de Araujo IE, Coelho MR, Kloth AD, Gainetdinov RR, Caron MG, Nicolelis MA, Simon SA (2007) Dopamine levels modulate the updating of tastant values. Genes Brain Behav 6:314-320
12. Davies W, Humby T, Kong W, Otter T, Burgoyne PS, Wilkinson LS (2009) Converging pharmacological and genetic evidence indicates a role for steroid sulfatase in attention. Biol Psychiatry 66:360-367
13. Donovan DM, Miner LL, Perry MP, Revay RS, Sharpe LG, Przedborski S, Kostic V, Philpot RM, Kirstein CL, Rothman RB, Schindler CW, Uhl GR (1999) Cocaine reward and MPTP toxicity: alteration by regional variant dopamine transporter overexpression. Brain Res Mol Brain Res 73:37-49
14. Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ (1999) Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet 354:2132-2133
15. Dresel S, Krause J, Krause KH, LaFougere C, Brinkbaumer K, Kung HF, Hahn K, Tatsch K (2000) Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment. Eur J Nucl Med 27:1518-1524
16. Fumagalli F, Racagni G, Colombo E, Riva MA (2003) BDNF gene expression is reduced in the frontal cortex of dopamine transporter knockout mice. Mol Psychiatry 8:898-899
17. Gainetdinov RR, Caron MG (2000) An animal model of attention deficit hyperactivity disorder. Mol Med Today 6:43-44
18. 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 40:380-382
19. Gainetdinov RR, Caron MG (2003) Monoamine transporters: from genes to behavior. Annu Rev Pharmacol Toxicol 43:261-284
20. 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 26:148-153
21. Gainetdinov RR, Jones SR, Caron MG (1999a) Functional hyperdopaminergia in dopamine transporter knock-out mice. Biol Psychiatry 46:303-311
22. 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 283:397-401
23. Gainetdinov RR, Mohn AR, Bohn LM, Caron MG (2001) Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. Proc Natl Acad Sci USA 98:11047-11054
24. Gainetdinov RR, Sotnikova TD, Caron MG (2002) Monoamine transporter pharmacology and mutant mice. Trends Pharmacol Sci 23:367-373
25. Galinanes GL, Taravini IR, Murer MG (2009) Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse. J Neurosci 29:2496-2509
26. Ghisi V, Ramsey AJ, Masri B, Gainetdinov RR, Caron MG, Salahpour A (2009) Reduced D2-mediated signaling activity and trans-synaptic upregulation of D1 and D2 dopamine receptors in mice overexpressing the dopamine transporter. Cell Signal 21:87-94
27. 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 379:606-612
28. Gizer IR, Ficks C, Waldman ID (2009) Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 126:51-90
29. Gordon I, Weizman R, Rosenne E, Rehavi M (1995) Developmental and age-related alterations in rat brain presynaptic dopaminergic mechanisms. Brain Res Dev Brain Res 85:225-228
30. 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 90:387-393
31. Hess EJ, Collins KA, Wilson MC (1996) Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. J Neurosci 16:3104-3111
32. Hironaka N, Ikeda K, Sora I, Uhl GR, Niki H (2004) Food-reinforced operant behavior in dopamine transporter knockout mice: enhanced resistance to extinction. Ann N Y Acad Sci 1025:140-145
33. Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG (1998) Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc Natl Acad Sci USA 95:4029-4034
34. Jones SR, Gainetdinov RR, Hu XT, Cooper DC, Wightman RM, White FJ, Caron MG (1999) Loss of autoreceptor functions in mice lacking the dopamine transporter. Nat Neurosci 2:649-655
35. Kalueff AV, Fox MA, Gallagher PS, Murphy DL (2007) Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice. Genes Brain Behav 6:389-400
36. Khan SA, Faraone SV (2006) The genetics of ADHD: a literature review of 2005. Curr Psychiatry Rep 8:393-397
37. Kostrzewa RM, Kostrzewa JP, Kostrzewa RA, Nowak P, Brus R (2008) Pharmacological models of ADHD. J Neural Transm 115:287-298
38. Kuhar MJ, Sanchez-Roa PM, Wong DF, Dannals RF, Grigoriadis DE, Lew R, Milberger M (1990) Dopamine transporter: biochemistry, pharmacology and imaging. Eur Neurol 30(Suppl 1):15-20
39. Lucki I (1998) The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44:151-162
40. Madras BK, Miller GM, Fischman AJ (2005) The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1397-1409
41. Markou A, Chiamulera C, Geyer MA, Tricklebank M, Steckler T (2009) Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology 34:74-89
42. Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998) Rodent data and general hypothesis: antipsychotic action exerted through 5-Ht2A receptor antagonism is dependent on increased serotonergic tone. J Neural Transm 105:365-396
43. McGough JJ, McCracken JT, Loo SK, Manganiello M, Leung MC, Tietjens JR, Trinh T, Baweja S, Suddath R, Smalley SL, Hellemann G, Sugar CA (2009) A candidate gene analysis of methylphenidate response in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry
44. Mill J (2007) Rodent models: utility for candidate gene studies in human attention-deficit hyperactivity disorder (ADHD). J Neurosci Methods 166:294-305
45. Morice E, Denis C, Giros B, Nosten-Bertrand M (2004) Phenotypic expression of the targeted null-mutation in the dopamine transporter gene varies as a function of the genetic background. Eur J Neurosci 20:120-126
46. Morice E, Billard JM, Denis C, Mathieu F, Betancur C, Epelbaum J, Giros B, Nosten-Bertrand M (2007) Parallel loss of hippocampal LTD and cognitive flexibility in a genetic model of hyperdopaminergia. Neuropsychopharmacology 32:2108-2116
47. Oliver PL, Davies KE (2009) Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk. Hum Mol Genet 18:4576-4589
48. Patel AP, Cerruti C, Vaughan RA, Kuhar MJ (1994) Developmentally regulated glycosylation of dopamine transporter. Brain Res Dev Brain Res 83:53-58
49. Pecina S, Cagniard B, Berridge KC, Aldridge JW, Zhuang X (2003) Hyperdopaminergic mutant mice have higher "wanting" but not "liking" for sweet rewards. J Neurosci 23:9395-9402
50. Powell SB, Lehmann-Masten VD, Paulus MP, Gainetdinov RR, Caron MG, Geyer MA (2004) MDMA "ecstasy" alters hyperactive and perseverative behaviors in dopamine transporter knockout mice. Psychopharmacology (Berl) 173:310-317
51. Ralph RJ, Paulus MP, Fumagalli F, Caron MG, Geyer MA (2001) Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knock-out mice: differential effects of D1 and D2 receptor antagonists. J Neurosci 21:305-313
52. Rocha BA, Goulding EH, O'Dell LE, Mead AN, Coufal NG, Parsons LH, Tecott LH (2002) Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytryptamine 2C receptor mutant mice. J Neurosci 22:10039-10045
53. Rodriguiz RM, Chu R, Caron MG, Wetsel WC (2004) Aberrant responses in social interaction of dopamine transporter knockout mice. Behav Brain Res 148:185-198
54. 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 90:991-1001
55. Russell VA (2007) Neurobiology of animal models of attentiondeficit hyperactivity disorder. J Neurosci Methods 161:185-198
56. Sagvolden T, Russell VA, Aase H, Johansen EB, Farshbaf M (2005) Rodent models of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1239-1247
57. Salahpour A, Medvedev IO, Beaulieu JM, Gainetdinov RR, Caron MG (2007) Local knockdown of genes in the brain using small interfering RNA: a phenotypic comparison with knockout animals. Biol Psychiatry 61:65-69
58. Salahpour A, Ramsey AJ, Medvedev IO, Kile B, Sotnikova TD, Holmstrand E, Ghisi V, Nicholls PJ, Wong L, Murphy K, Sesack SR, Wightman RM, Gainetdinov RR, Caron MG (2008) Increased amphetamine-induced hyperactivity and reward in mice overexpressing the dopamine transporter. Proc Natl Acad Sci USA 105:4405-4410
59. Shen HW, Hagino Y, Kobayashi H, Shinohara-Tanaka K, Ikeda K, Yamamoto H, Yamamoto T, Lesch KP, Murphy DL, Hall FS, Uhl GR, Sora I (2004) Regional differences in extracellular dopamine and serotonin assessed by in vivo microdialysis in mice lacking dopamine and/or serotonin transporters. Neuropsychopharmacology 29:1790-1799
60. Siesser WB, Cheng SY, McDonald MP (2005) Hyperactivity, impaired learning on a vigilance task, and a differential response to methylphenidate in the TRbetaPV knock-in mouse. Psychopharmacology (Berl) 181:653-663
61. 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 5:282-297
62. Sora I, Wichems C, Takahashi N, Li XF, Zeng Z, Revay R, Lesch KP, Murphy DL, Uhl GR (1998) Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci USA 95:7699-7704
63. Sotnikova TD, Beaulieu JM, Barak LS, Wetsel WC, Caron MG, Gainetdinov RR (2005) Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease. PLoS Biol 3:e271
64. Spielewoy C, Biala G, Roubert C, Hamon M, Betancur C, Giros B (2001) Hypolocomotor effects of acute and daily d-amphetamine in mice lacking the dopamine transporter. Psychopharmacology (Berl) 159:2-9
65. Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, Taylor E, Casey BJ, Castellanos FX, Wadhwa PD (2007) Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev 17:39-59
66. Tilley MR, Cagniard B, Zhuang X, Han DD, Tiao N, Gu HH (2007) Cocaine reward and locomotion stimulation in mice with reduced dopamine transporter expression. BMC Neurosci 8:42
67. Torres GE, Gainetdinov RR, Caron MG (2003) Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci 4:13-25
68. van der Kooij MA, Glennon JC (2007) Animal models concerning the role of dopamine in attention-deficit hyperactivity disorder. Neurosci Biobehav Rev 31:597-618
69. Volkow ND, Wang GJ, Newcorn J, Fowler JS, Telang F, Solanto MV, Logan J, Wong C, Ma Y, Swanson JM, Schulz K, Pradhan K (2007) Brain dopamine transporter levels in treatment and drug naive adults with ADHD. Neuroimage 34:1182-1190
70. Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH, Telang F, Fowler JS, Zhu W, Logan J, Ma Y, Pradhan K, Wong C, Swanson JM (2009) Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA 302:1084-1091
71. Winstanley CA, Theobald DE, Dalley JW, Robbins TW (2005) Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders. Neuropsychopharmacology 30:669-682
72. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21:1787-1794
73. Xu F, Gainetdinov RR, Wetsel WC, Jones SR, Bohn LM, Miller GW, Wang YM, Caron MG (2000) Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 3:465-471
74. Yan TC, McQuillin A, Thapar A, Asherson P, Hunt SP, Stanford SC, Gurling H (2010) NK1 (TACR1) receptor gene 'knockout' mouse phenotype predicts genetic association with ADHD. J Psychopharmacol 24:27-38
75. Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Cyr M, Beaulieu JM, Torres GE, Grant SG, Caron MG (2004) Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 41:625-638
76. Young JW, Light GA, Marston HM, Sharp R, Geyer MA (2009) The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS One 4:e4227
77. Zhuang X, Oosting RS, Jones SR, Gainetdinov RR, Miller GW, Caron MG, Hen R (2001) Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc Natl Acad Sci USA 98:1982-1987
78. Zoli M, Jansson A, Sykova E, Agnati LF, Fuxe K (1999) Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol Sci 20:142-150