Abstract
Several studies involving postnatal administration of the N-methyl-D-aspartate (NMDA) antagonists, dizocilpine (MK-801; 3 x 0.5 mg/kg, at 08.00, 16.00 and 24.00 h) on Postnatal day 11, or Ketamine (1 × 50 mg/kg) or Ethanol (1 × 2.5 g/kg, Ethanol-Low, or 2 × 2.5 g/kg, 2-h interval, Ethanol-High) on Postnatal day 10, are described. Some mice from each treatment/vehicle group were sacrificed 24 h after NMDA antagonist treatment and brain regions were taken for fluoro-jade staining analysis. Functional analysis was initiated at 60 days of age. All three treatments inducing an antagonistic action at NMDA receptors, MK-801, Ketamine and Ethanol-High induced a similar pattern of initial hypoactivity followed by marked and lasting hyper-activity in the motor activity test chambers. In each case, the basal hyperactivity level was abolished by acute treatment with a low dose of D-amphetamine (0.25 mg/kg). All three treatments, MK-801, Ketamine and Ethanol-High, induced a deficit in acquisitive performance in the radial arm maze test of instrumental learning. The deficit induced by postnatal MK-801 was abolished by acute treatment with the low dose of D-amphetamine. All three treatments, MK-801, Ketamine and Ethanol-High, resulted in normal acquisitive performance during the first three test days in the circular swim with the submerged platform maintained in a constant position, but on the fourth test day, with the platform position shifted to a different “quadrant”, induced marked deficits. Fluoro-jade staining analyses indicated a devastating cell degeneration in several brain regions of mice administered NMDA antagonists postnatally, including the hippocampus, frontal cortex, parietal cortex, and cerebellum. Severe cell degeneration in the laterodorsal thalamus due to Ethanol or diazepam (5 mg/kg) appeared not to affect the different aspects of function. The pattern of dysfunctional outcome and apoptotic cell loss following postnatal NMDA antagonist treatment offers a plausible similarity to the major aspects of ‘syndromatic continuity’ in ADHD, hyperactivity, inattention and impulsivity, thereby providing an interesting animal model of the disorder.
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Adler LE, A Olincy, M Waldo, JG Harris, J Griffith, K Stevens, K Flach, H Nagamoto, P Bickford, S Leonard and R Freedman (1998) Schizophrenia, sensory gating, and nicotinic receptors.Schizophr. Bull. 24, 189–202.
Adler LE, A Olincy, E Cawthra, M Hoffer, HT Nagamoto, L Amass and R Freedman (2001) Reversal of diminished inhibitory sensory gating in cocaine addicts by nicotinic cholinergic mechanism.Neuropsychopharmacology 24, 671–679.
Archer T, A Fredriksson, G Jönsson, T Lewander, AK Mohammed, SB Ross and U Söderberg (1986) Central noradrenaline depletion antagonizes aspects of D-amphetamine-induced hyperactivi-ty in the rat.Psychopharmacology (Berl.) 88, 141–146.
Archer T, T Palomo and A Frediksson (2002a) Functional deficits following neonatal dopamine depletion and isolation housing: circular water maze acquisition under pre-exposure conditions and motor activity.Neurotoxicity Res. 4, 503–522.
Archer T, T Palomo and A Frediksson (2002b) Neonatal 6-hydrox-ydopamine-induced hypo/hyperactivity: blockade by dopamine reuptake inhibitors and effect of acute D-amphetamine.Neurotoxicity Res. 4, 503–522.
Aultman JM and B Moghaddam (2001) Distinct contributions of glutamate and dopamine receptors to temporal aspects of rodent working memory using a clinically relevant task.Psychopharmacology 153, 353–364.
Barkley RA (1997) Behavioural inhibition, sustained attention and executive functions: constructing a unifying theory of ADHD.Psychol. Bull. 121, 65–94.
Barkley RA (1977) A review of stimulant drug research with hyperactive children.J. Child Psychol. Psychiatry 18, 137–165.
Barkley RA (2002) Major life activity and health outcomes associated with attention-deficit/hyperactivity disorder.J. Clin. Psychiatry 63 Suppl. 12, 10–15.
Barkley RA, M Fischer, CS Edelbrock and L Smallish (1990) The adolescent outcome of hyperactive children diagnosed by research criteria. I. An 8-year prospective follow-up study.J. Am. Acad. Child Adolesc. Psychiatry 29, 546–557.
Barkley RA, GJ DuPaul and MB McMurray (1991) Attention deficit disorder with and without hyperactivity: clinical response to three different doses of methylphenidate.Pediatrics 87, 519–531.
Barkley RA, M Fisher, L Smallish and K Fletcher (2002) The persistence of attention-deficit/hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder.J. Abnorm. Psychol. 111, 279–289.
Berquin PC, JN Giedd, LK Jacobsen, SD Hamburger, AL Krain, JL Rapoport and FX Castellanos (1998) Cerebellum in attention-deficit hyperactivity disorder — a morphometric MRI study.Neurology 50, 1087–1093.
Biederman J and T Spencer (1999) Attention-defict/hyperactivity disorder (ADHD) is a noradrenergic disorder.Biol. Psychiatry 46, 1234–1242.
Biederman J, RJ Baldessarini, V Wright, D Knee and JS Harmatz (1989) A double-blind placebo controlled study of desipramine in the treatment of ADD I. Efficacy.J. Am. Acad. Child Adolesc. Psychiatry 28, 777–784.
Biederman J, J Newcorn and S Sprich (1991) Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders.Am. J. Psychiatry 148, 564–577.
Braff DL, MA Geyer and NR Swerdlow (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.Psychopharmacology 156, 234–258.
Bush G, JA Frazier, SL Rauch, LJ Seidman, PJ Whalen, MA Jenike, BR Rosen and J Biederman (1999) Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.Biol. Psychiatry 45, 1542–1552.
Bymaster FP, JS Katner, DL Nelson, SK Hemrick-Luecke, PG Threlkeld, JH Heiligenstein, SM Morin, DR Gehlert and KW Perry (2002) Atomoxetine increases extracellular levels of nor-epinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder.Neuropsychopharmacology 27, 699–711.
Byrnes ML, JN Reynolds and JF Brien (2001) Effect of prenatal ethanol exposure during the brain growth spurt of the guinea pig.Neurotoxicol. Teratol. 23, 355–364.
Carlsson ML (2000) On the role of cortical glutamate in obsessive-compulsive disorder and attention-deficit hyperactivity disorder, two phenomenologically antithetical conditions.Acta Psychiatr. Scand. 102, 401–413.
Carlsson ML (2001) On the role of prefrontal cortex glutamate for the antithetical phenomenology of obsessive compulsive disorder and attention deficit hyperactivity disorder.Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 5–26.
Carrey N, FP MacMaster, S Sparkes, SC Khan and V Kusumakar (2002) Glutamatergic changes with treatment in attention deficit hyperactivity disorder: a preliminary case series.J. Child Adolesc. Psychopharmacol. 12, 331–336.
Carrey N, FP MacMaster, J Fogel, S Sparkes, D Waschbusch, S Sullivan and M Schmidt (2003) Metabolite changes resulting from treatment in children with ADHD: a 1H-MRS study.Clin. Neuropharmacol. 26, 218–221.
Castellanos FX, J Elia, MJ Kruesi, WL Marsh, CS Gulotta, WZ Potter, GF Ritchie, SD Hanburger and JL Rapoport (1996a) Cerebrospinal fluid homovanillic acid predicts behavioural response to stimulants in 45 boys with attention deficit/hyperac-tivity disorder.Neuropsychopharmacology 14, 125–137.
Castellanos FX, JN Giedd, WL Marsh, SD Hamburger, AC Vaituzis, DP Dickstein, SE Sarfatti, YC Vauss, JW Snell, N Lange, D Kaysen, AL Krain, GF Ritchie, JC Rajapakse and JL Rapoport (1996b) Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder.Arch. Gen. Psychiatry 53, 607–616.
Chen WA, SE Parnell and JR West (1999) Early postnatal alcohol exposure produced long-term deficits in brain weight, but not the number of neurons in the locus coeruleus.Brain Res. Dev. Brain Res. 118, 33–38.
Clarren SK and DW Smith (1978) The fetal alcohol syndrome.New Engl. J. Med. 298, 1063–1067.
Davids E, K Zhang, FI Tarazi and RJ Baldessarini (2003) Animal models of attention-deficit hyperactivity disorder.Brain Res. Brain Res. Rev. 42, 1–21.
Davison AN and J Dobbing (1968)Applied Neurochemistry (Blackwell: Oxford), pp 253–316.
Dougherty DD, AA Bonab, TJ Spencer, SL Rauch, BK Madras and AJ Fischman (1999) Dopamine transport density in patients with attention deficit hyperactivity disorder.Lancet 354, 2132–2133.
Downey KK, FW Stelson, OF Pomerleau and B Giordani (1997) Adult attention deficit hyperactivity disorder: psychological test profiles in a clinical population.J. Nerv. Ment. Dis. 185, 32–38.
Dresel S, J Krause, K-H Krause, C LaFougere, K Brinkbaumer, HF Kung, K Hahn and K Tatsch (2000) Attention deficit hyperactiv-ity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate.Eur. J. Nucl. Med. 27, 1518–1524.
Eckardt MJ, SE File, GL Gessa, KA Grant, C Guerri, PL Hoffman, H Kalant, GF Koob, TK Li and B Tabakoff (1998) Effects of moderate alcohol consumption on the central nervous system.Alcohol Clin. Exp. Res. 22, 998–1040.
Elia J, BG Borcheding, JL Rapoport and CS Keysor (1991) Methylphenidate and dextroamphetamine treatments of hyperac-tivity: Are there true responders?Psychiatry Res. 36, 141–155.
Elia J, P Ambrosini and JL Rapoport (1999) Treatment of attention-deficit hyperactivity disorder.New Engl. J. Med. 340, 780–788.
Ercan ES, H Coskunol, A Varan and K. Toksoz (2003) Childhood attention deficit/hyperactivity disorder and alcohol dependence: a 1-year follow-up.Alcohol Alcohol. 38, 352–356.
Ernst M, AJ Zametkin, JA Matochik, D Pascualvaca, PH Jons and RM Cohen (1999) High midbrain [18F]DOPA accumulation in children with attention deficit hyperactivity disorder.Am. J. Psychiatry 156, 1209–1215.
Ernst M, AS Kimes, ED London, JA Matochik, D Eldreth, S Tata, C Contoreggi, M Leff and K Bolla (2003) Neural substrates of decision making in adults with attention deficit hyperactivity disorder.Am. J. Psychiatry 160, 1061–1070.
Famy C, AP Streissguth and AS Unis (1998) Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects.Am. J. Psychiatry 155, 552–554.
Faraone SV, J Biederman, WJ Chen, S Milberger, R Warburton and MT Tsuang (1995) Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): gender, psychiatric comorbidity, and maternal ADHD.J. Abnorm. Psychol. 104, 334–345.
Faraone SV, J Biederman, D Mennin, R Russell and MT Tsuang (1998) Familial subtypes of attention deficit hyperactivity disor der: a 4-year follow-up study of children from antisocial-ADHD families.J. Child Psychol. Psychiatry 39, 1045–1053.
Faraone SV, MC Monuteaux, J Biederman, SL Cohan and E. Mick (2003) Does parental ADHD bias maternal reports of ADHD symptoms in children?J. Consult. Clin. Psychol. 71, 168–175.
Filipek PA, M Semrud-Clikeman, RJ Steingard, PF Renshaw, DN Kennedy and J Biederman (1997) Volumetric MRI analysis comparing attention-deficit hyperactivity disorder and normal controls.Neurology 48, 589–601.
Fisher SE, C Francks, JT McCracken, JJ McGough, AJ Marlow, IL MacPhie, DF Newbury, LR Crawford, CG Palmer, JA Woodward, M Del’Homme, DP Cantwell, SF Nelson, AP Monaco and SL Smalley (2002) A genomewide scan for loci involved in attention-deficit/hyperactivity disorder.Am. J. Hum. Genet. 70, 1183–1196.
Fredriksson A and T Archer (1996) Alpha-phenyl-tert-butyl-nitrone (PBN) reverses age-related maze learning performance and motor activity deficits in C57 Bl/6 mice.Behav. Pharmacol. 7, 245–253.
Fredriksson A and T Archer (2002) Functional alteration by NMDA antagonist: effects of L-Dopa, neuroleptic drugs and postnatal administration.Amino Acids 25, 111–132.
Fredriksson A and T Archer (2003) Hyperactivity following postnatal NMDA antagonist treatment: reversal by d-amphetamine.Neurotoxicity Res. 5(7), 549–564.
Fredriksson A, T Archer, H Alm, T Gordh and P Eriksson (2004) Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration.Behav Brain Res. 153(2), 367–376.
Fredriksson A, N Schröder, P Eriksson, I Izquierdo and T Archer (1999) Neonatal iron exposure induces neurobehavioural dys functions in adult mice.Toxicol. Appl. Pharmacol. 159, 25–30.
Fredriksson A, N Schröder, P. Eriksson, I Izquierdo and T Archer (2000) Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period.Brain Res. Dev. Brain Res. 119, 65–74.
Fredriksson A, N Schröder, P Eriksson, I Izquierdo and T Archer (2001) Neonatal iron potentiates adult MPTP-induced neurode-generative and functional deficits.Parkinsonism Relat. Dis. 7, 97–105.
Fredriksson A, T Archer, H Alm, T Gordh and P Eriksson (2003) Neurofunctional deficits and potentiated apoptosis by neonatal NMDA administration.Behav. Brain Res. 153(2), 367–376.
Frick PJ, K Kuper, P Silverthorn and M Cotter (1995) Antisocial behaviour, somatization, and sensation-seeking behaviour in mothers of clinic-referred children.J. Am. Acad. Child Adolesc. Psychiatry 34, 805–812.
Garces K (2003) Atomoxetine for attention deficit/hyperactivity disorder.Issues Emerg. Health Technol. 46, 1–4.
Gorter JA and JP de Bruin (1992) Chronic neonatal MK-801 results in an impairment of spatial learning performance in the adult rat.Brain Res. 580, 12–17.
Griffith JM, JE O’Neill, F Petty, D Garver, D Young and R Freedman (1998) Nicotinic receptor desensitization and sensory gating deficits in schizophrenia.Biol. Psychiatry 44, 98–106.
Hawi Z, M Dring, A Kirley, D Foley, L Kent, N Craddock, P Asherson, S Curran, A Gould, S Richards, D Lawson, H Pay, D Turic, K Langley, M Owen, M O’Donovan, A Thapar, M Fitzgerald and M Gill (2002) Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample.Mol. Psychiatry 7, 718–725.
Ikonomidou C, F Bosch, M Miksa, P Bittigau, J Vockler, K Dikranian, TI Tenkova, V Stefovska and JW Olney (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain.Science 283, 70–74.
Ikonomidou C, P Bittigau, MJ Ishimaru, DF Wozniak, C Koch, K Genz, MT Price, V Stefovska, F Horster, T Tenkova, K Dikranian and JW Olney (2000) Ethanol induced apoptotic neurodegenera-tion and fetal alcohol syndrome.Science 287, 1056–1060.
Ikonomidou C, P Bittigau, C Koch, K Genz, MT Price, F Hörster, U Felderhoff-Mueser, TI Tenkova, K Dikranian and JW Olney (2001) Neurotransmitters and apoptosis in the developing brain.Biochem. Pharmacol. 62, 401–405.
Ishimaru MJ, C Ikonomidou, TI Tenkova, TC Der, K Dikranian, MA Sesma and JW Olney (1999) Distinguishing excitotoxic from apoptotic neurodegeneration in the developing rat brain.J. Comp. Neurol. 408, 461–476.
Jones MD and EJ Hess (2003) Norepinephrine regulates locomotor hyperactivity in the mouse mutant coloboma.Pharmacol. Biochem. Behav. 75, 209–216.
Kalat JW (2001)Biological Psychology (Wadsworth/Thomson Learning: Belmont, CA).
Kirk RE (1995)Experimental Design. Procedures in Behavioural Science (Brooks/Cole: Belmont, CA).
Kotimaa AJ, I Moilanen, A Taanila, H Ebeling, SL Smalley, G McGough, AL Hartikainen and MR Jarvelin. (2003) Maternal smoking and hyperactivity in 8-year-old children.J. Am. Acad. Child Adolesc. Psychiatry 42, 826–833.
Kratochvil CJ, BS Vaughan, MJ Harrington and WJ Burke (2003) Atomoxetine, a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder.Expert Opin. Pharmacother. 4, 1165–1174.
Krause K-H, SH Dresel, J Krause, HF Kung and K Tatsch (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, 107–110.
Krause K-H, SH Dresel, J Krause, HF Kung, K Tatsch and M Ackenheil (2002) Stimulant-like action of nicotine on striatal dopamine transporter in the brain of adults with attention deficit hyperactivity disorder.Int. J. Neuropsychopharmacology 5, 111–113.
Linnet KM, S Dalsgaard, C Obel, K Wisborg, TB Henriksen, A Rodriguez, A Kotimaa, I Moilanen, PH Thomsen, J Olsen and MR Jarvelin (2003) Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviours: review of the current evidence.Am. J. Psychiatry 160, 1028–1040.
Lopez RE (1965) Hyperactivity in twins.Can. Psychiatr. Assoc. J. 10, 421–426.
Lou HC, L Henricksen, P Bruhn, H Borner and JB Nielsen (1989) Striatal dysfunction in attention deficit and hyperkinetic disorder.Arch. Neurol. 46, 48–52.
Lynam DR (1996) Early identification of chronic offenders: Who is the fledgling psychopath?Psychol. Bull. 120, 209–234.
Lynam DR (1998) Early identification of the fledgling psychopath: locating the psychopathic child in the current nomenclature.J. Abnorm. Psychol. 107, 566–575.
Madras B (2002) Brain imaging of the dopamine transporter in ADHD.Behav. Brain Res. 130, 57–63.
Mailman RB, MH Lewis and CD Kilts (1981) Animal models related to developmental disorders: theoretical and pharmacological analyses.Appl. Res. Ment. Retard. 2, 1–12.
Manuzza S, RG Klein, A Bessler, P Malloy and M LaPadula (1993) Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status.Arch. Gen. Psychiatry 50, 565–576.
Manuzza S, RG Klein, A Bessler, P Malloy and M LaPadula (1998) Adult psychiatric status of hyperactive boys grown up.Arch. Gen. Psychiatry 55, 493–498.
Mariani MA and RA Barkley (1997) Neuropsychological and academic functioning in preschool boys with attention deficit hyper-activity disorder.Dev. Psychol. 13, 111–129.
Michelson D, L Adler, T Spencer, FW Reimherr, SA West, AJ Allen, D Kelsey, J Wernicke, A Dietrich and D Milton (2003) Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies.Biol. Psychiatry 53, 112–120.
Mickley GA, DR Remmers-Roeber, C Crouse and R Peluso (2000) Ketamine blocks a taste recognition memory in fetal rats.Pharmacol. Biochem. Behav. 67, 575–581.
Mickley GA, DR Remmers-Roeber, CM Dengler, CL Kenmuir and C Crouse (2001) Paradoxical effects of ketamine on the memory of fetuses of different ages.Brain Res. Dev. Brain Res. 127, 71–76.
Moghaddam B, B Adams, A Verma and D Daly (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.J. Neurosci. 17, 2921–2927.
Morris RGM (1983) An attempt to dissociate “spatial-mapping” from “working-memory”. Theories of hippocampal function, InNeurobiology of the Hippocampus (Seifert W, Ed.), (Academic Press: London), pp 405–432.
Mostofsky SH, AL Reiss, P Lockhart and MB Denckla (1998) Evaluation of cerebellar size in attention-deficit hyperactivity disorder.J. Child Neurol. 13, 434–439.
Nieoullon A (2002) Dopamine and the regulation of cognition and attention.Prog. Neurobiol. 67, 53–83.
Olney JW, J Labruyere and MT Price (1989) Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs.Science 244, 1360–1362.
Olney JW, DF Wozniak, V Jevtovic-Todorovic and C Ikonomidou (1991) NMDA antagonist neurotoxicity: mechanism and prevention.Science 254, 1515–1518.
Olney JW, NB Farber, DF Wozniak, V Jevtovic-Todorovic and C Ikonomidou (2000) Environmental agents that have the potential to trigger massive apoptotic neurodegeneration in the developing brain.Environ. Health Prospect. 108 (Suppl. 3), 383–388.
Olney JW, TI Tenkova, K Dikranian, YQ Qin, J Labruyere and C Ikonomidou (2002a) Ethanol-induced apoptotic neurodegenera-tion in the developing C57BL/6 mouse brain.Brain Res. Dev. Brain Res. 133, 115–126.
Olney JW, DF Wozniak, V Jevtovic-Todorovic, NB Farber, P Bittigau and C Ikonomidou (2002b) Glutamate and GABA receptor dysfunction in the fetal alcohol syndrome.Neurotoxicity Res. 4, 315–325.
Olton DS and MA Werz (1978) Hippocampal function and behaviour: spatial discrimination and response inhibition.Physiol. Behav. 20, 597–605.
Olton DS, JA Walker and FH Gage (1978) Hippocampal connections and spatial discrimination.Brain Res. 139, 295–308.
Palomo T, RJ Beninger, RM Kostrzewa and T Archer (2003) Brain sites of movement disorder: genetic and environmental agents in neurodevelopmental perturbations.Neurotoxicity Res. 5, 1–26.
Panksepp J, J Burgdorf, C Turner and N Gordon (2003) Modeling ADHD-type arousal with unilateral frontal cortex damage in rats and beneficial effects of play therapy.Brain Cogn. 52, 97–105.
Pomerleau OF, KK Downey, FW Stelson and CS Pomerleau (1995) Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder.J. Subst. Abuse 7, 373–378.
Raol YH, DR Lynch and AR Brooks-Kayal (2001) Role of excitatory amino acids in developmental epilepsies.Ment. Retard. Dev. Disabil. Res. Rev. 7, 254–260.
Rapport MD, KM Chung, G Shore, CB Denney and P Isaacs (2000) Upgrading the science and technology of assessment and diagnosis: laboratory and clinic-based assessment of children with ADHD.J. Clin. Child Psychol. 29, 555–568.
Retz W, J Thome, D Blocher, M Baader and M Rosler (2002) Association of attention deficit hyperactivity disorder-related psychopathology and personality traits with the serotonin transporter promoter region polymorphism.Neurosci. Lett. 319, 133–136.
Riva CJ and G Giorgi (2000) The cerebellum contributes to higher functions during development: evidence from: series of children surgically treated for posterior fossa tumours.Brain 123, 1051–1061.
Roegge CS, BW Seo, KM Crofton and SL Schantz (2000) Gestation-lactation exposure to Aroclor 1254 impairs radial-arm maze performance in male rats.Toxicol. Sci. 57, 121–130.
Rohde LA, T Roman, C Szobot, RD Cunha, MH Hutz and J Biederman (2003) Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: a pilot study.Synapse 48, 87–89.
Roman T, C Szobot, S Martins, J Biederman, LA Rohde and MH Hutz (2002a) Dopamine transporter gene and response to methylphenidate in attention-deficit/hyperactivity disorder.Pharmacogenetics 12, 497–499.
Roman T, M Schmitz, GV Polanczyk, M Eizirik, LA Rohde and MH Hutz (2002b) Further evidence for the association between attention-deficit/hyperactivity disorder and the dopamine-beta-hydroxylase gene.Am. J. Med. Genet. 114, 154–158.
Rubia K, J Oosterlaan, JA Sergeant, D Brandeis and T Leeuwen (1998) Inhibitory dysfunction in hyperactive boys.Behav. Brain Res. 94, 25–32.
Rubia K, S Overmeyer, E. Taylor, M. Brammer, SC Williams, A. Simmons and ET Bullmore (1999) Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI.Am. J. Psychiatry 156, 891–896.
Russell VA (2003)In vitro glutamate-stimulated release of dopamine from nucleus accumbens core and shell of spontaneous hypertensive rats.Metab. Brain Dis. 18, 161–168.
Russell VA and TM Wiggins (2000) Increased glutamate-stimulat-ed norepinephrine release from prefrontal cortex slices of spontaneously hypertensive rats.Metab. Brain Res. 15, 297–304.
Sadile AG, MP Pellicano, T Sagvolden and JA Sergeant (1996) NMDA and non-NMDA sensitive [L-3H]glutamate receptor binding in the brain of the Naples high- and low-excitability rats: an autoradiographical study.Behav. Brain Res. 78, 163–174.
Saules KK, CS Pomerleau and H Schubiner (2003) Patterns of inattentive and hyperactive symptomatology in cocaine-addicted and non-addicted smokers diagnosed with adult attention deficit hyperactivity disorder.J. Addict. Dis. 22, 71–78.
Schachar R and R Wachsmuth (1990) Hyperactivity and parental psychopathology.J. Child Psychol. Psychiatry 31, 381–392.
Schmued LC and KJ Hopkins (2000) Fluoro-Jade: novel fluo-rochromes for detecting toxicant induced neuronal degeneration.Toxicol. Pathol. 28, 91–99.
Schmued LC, C Albertson and W Slikker (1997) Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration.Brain Res. 751, 37–46.
Schweitzer JB, TL Faber, ST Grafton, LE Tune, JM Hoffman and CD Kilts (2000) Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder.Am. J. Psychiatry 157, 278–280.
Schweitzer JB, DO Lee, RB Hanford, MA Tagamets, JM Hoffman, ST Grafton and CD Kilts (2003) A positron emission tomography study of methylphenidate in adults with ADHD: alterations in resting blood flow and predicting treatment response.Neuropsychopharmacology 28, 967–973.
Shaywitz BA, HH Klopper, RD Yager and JW Gordon (1976) Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine.Nature 261, 153–155.
Shaywitz BA, JW Gordon, HH Klopper and DA Zelterman (1977) The effect of 6-hydroxydopamine on habituation of activity in the developing rat pup.Pharmacol. Biochem. Behav. 6, 391–396.
Sherman DK, WG Iacono and MK McGue (1997a) Attention-deficit hyperactivity disorder dimensions: a twin study of inattention and impulsivity-hyperactivity.J. Am. Acad. Child Adolesc. Psychiatry 36, 745–753.
Sherman DK, MK McGue and WG Iacono (1997b) Twin concordance for attention deficit hyperactivity disorder: a comparison of teachers’ and mothers’ reports.Am. J. Psychiatry 154, 532–535.
Simpson D and CM Perry (2003) Atomoxetine.Paediatr. Drugs 5(6), 407–415.
Smalley SL, V Kustanovich, SL Minassian, JL Stone, MN Ogdie, JJ McGough, JT McCracken, IL MacPhie, C Francks, SE Fisher, RM Cantor, AP Monaco and SF Nelson (2002) Genetic linkage of attention-deficit hyperactivity disorder on chromosome 16p13, in a region implicated in autism.Am. J. Hum. Genet. 71, 959–963.
Solanto MV (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration.Behav. Brain Res. 94, 127–152.
Solanto MV (2002) Dopamine dysfunction in AD/HD: integrating clinical and basic science research.Behav. Brain Res. 130, 65–71.
Spencer T, T Wilens, J Biederman, SV Faraone, S Ablon and K Lapey (1995) A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention deficit hyperactivity disorder.Arch. Gen. Psychiatry 52, 434–443.
Spencer T, J Biederman, T Wilens, M Harding, D O’Donnell and S Griffin (1996) Pharmacotherapy of attention-deficit hyperactivi-ty disorder across the life cycle.J. Am. Acad. Child Adolesc. Psychiatry 35, 409–432.
Spencer T, J Biederman, T Wilens, J Prince, M Hatch, J Jones, M Harding, SV Faraone and L Seidman (1998) Effectiveness and tolerability of atomoxetine in adults with attention deficit hyper-activity disorder.Am. J. Psychiatry 155, 693–695.
Spencer T, J Biederman, J Heiligenstein, T Wilens, D Faries, J Prince, SV Faraone, J Rea, J Witcher and S Zervas (2001) An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder.J. Child Adolesc. Psychopharmacol. 11, 251–265.
Sprich S, J Biederman, MH Crawford, E Mundy and SV Faraone (2000) Adoptive and biological families of children and adolescents with ADHD.J. Am. Acad. Child Adolesc. Psychiatry 39, 1432–1437.
Swanson JM, JA Sergeant, E Taylor, EJS Sonuga-Barke, PS Jensen and DP Cantwell (1998) Attention deficit hyperactivity disorder and hyperkynetic disorder.Lancet 351, 329–343.
Swanson JM, P Flodman, J Kennedy, MA Spence, R Moyzis, S Schuck, M Murias, J Moriaty, C Barr, M Smith and M Posner (2000) Dopamine genes and ADHD.Neurol. Biobehav. Rev. 24, 21–25.
Szatmari P (1992) The epidemiology of attention-deficit hyperac-tivity disorder.Child Adolesc. Psychiatry Clin. North Am. 1, 361–371.
Vaidya CJ, G Austin, G. Kirkorian, HW Ridlehuber, JE Diamond, GH Glover and JD Gabrieli (1998) Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study.Proc. Natl. Acad. Sci. USA 95, 14494–14499.
Van Dyck CH, DM Quinlan, LM Cretella, JK Staley, RT Malison, RM Baldwin, JP Seibyl and RB Innis (2002) Unaltered dopamine transporter availability in adult attention deficit hyperactivity disorder.Am. J. Psychiatry 159, 309–312.
Verma A and B Moghaddam (1996) NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by DA.J. Neurosci. 16, 373–379.
Viggiano D, G Grammatikopoulos and A Sadile (2002) A morpho-metric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD.Behav. Brain Res. 130, 181–189.
Volkow ND, G Wang G, JS Fowler, SJ Gatley, J Logan, Y-S Ding, R Hitzemann and N Pappas (1998) Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate.Am. J. Psychiatry 155, 1325–1331.
Volkow ND, G Wang, JS Fowler, J Logan, M Gerasimov, L Maynard, Y-S Ding, SJ Gatley, A Gifford and D Franceschi (2001) Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.J. Neurosci. 21, RC121, 1–5.
Weiss G and L Hechtman (1979) The hyperactive child syndrome.Science 205, 1348–1354.
Weiss M and C Murray (2003) Assessment and management of attention-deficit hyperactivity disorder in adults.Cmaj. 168, 715–722.
Weiss M, L Hechtman and G Weiss (2000) ADHD in parents.J. Am. Acad. Child Adolesc. Psychiatry 39, 1059–1061.
West JR, CR Goodlett, DJ Bonthius and DR Pierce (1989) Manipulating peak blood alcohol concentrations in neonatal rats: review of an animal model for alcohol-related developmental effects.Neurotoxicology 10, 347–365.
West JR, WJ Chen and NJ Pantazis (1994) Fetal alcohol syndrome: the vulnerability of the developing brain and possible mechanisms of damage.Metab. Brain Dis. 9, 291–322.
Whalen PJ, G Bush, RJ McNally, S Wilhelm, SC McInerney, MA Jenike and SL Rauch (1998) The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division.Biol. Psychiatry 44, 345–348.
Wilens TE and TJ Spencer (2000) The stimulants revisited.Child Adolesc. Clin. North Am. 9, 573–603.
Wilens TE, J Biederman, J Prince, TJ Spencer, SV Faraone, R Warburton, D Schleifer, M Harding, C Linehan and D Geller (1996) Six-week, double-blind, placebo controlled study of desipramine for adult attention deficit hyperactivity disorder.Am. J. Psychiatry 153, 1147–1153.
Wilens TE, J Biederman, TJ Spencer, J Bostic, J Prince, MC Monuteaux, J Soriano, C Fine, A Abrams, M Rater and D Polisner (1999) A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder.Am. J. Psychiatry 156, 1931–1937.
Winsberg BG, DC Javitt and GS Silipo (1999) Electrophysiological indices of information processing in methylphenidate respon-ders.Biol. Psychiatry 42, 434–445.
Wishaw IQ (1985) Formation of a place learning-set by the rat: a new paradigm for neurobehavioural studies.Physiol. Behav. 35, 139–143.
Zametkin AJ and JL Rapoport (1987) Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years?J. Am. Acad. Child Adolesc. Psychiatry 26, 676–686.
Zametkin AJ, TE Nordahl, M Gross, AC King, WE Semple, J Rumsey, S Hamburger and RM Cohen (1990) Cerebral glucose metabolism in adults with hyperactivity of childhood onset.New Engl. J. Med. 323, 1361–1366.
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Fredriksson, A., Archer, T. Neurobehavioural deficits associated with apoptotic neurodegeneration and vulnerability for ADHD. neurotox res 6, 435–456 (2004). https://doi.org/10.1007/BF03033280
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DOI: https://doi.org/10.1007/BF03033280