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Psychopharmacological approaches to modulating attention in the five-choice serial reaction time task: implications for schizophrenia

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Abstract

Rationale

In schizophrenia, attentional disturbance is a core feature which may not only accompany the disorder, but may precede the onset of psychiatric symptoms.

Objectives

The five-choice serial reaction time task (5CSRTT) is a test of visuo-spatial attention that has been used extensively in rats for measuring the effects of systemic and central neurochemical manipulations on various aspects of attentional performance, including selective attention, vigilance and executive control. These findings are relevant to our understanding of the neural systems that may be compromised in patients with schizophrenia.

Methods

The 5CSRTT is conducted in an operant chamber that has multiple response locations, in which brief visual stimuli can be presented randomly. Performance is maintained using food reinforcers to criterion levels of accuracy. Various aspects of performance are measured, including attentional accuracy and premature responding, especially under different attentional challenges.

Results

The effects of systemic and intra-cerebral infusions of selective dopamine, serotonin and cholinergic receptor agents on the 5CSRTT are reviewed with a view to identifying attention-enhancing effects that may be relevant to the treatment of cognitive deficits in schizophrenia. In addition, some novel agents such as modafinil and histamine receptor agents are also considered. Examining the effects of selective neurochemical lesions helped define the neural locus of attentional effects. Similarly, findings from microdialysis studies helped identify the extracellular changes in neurotransmitters and their metabolites in freely moving rats during performance of the 5CSRTT.

Conclusions

The monoaminergic and cholinergic systems have independent but complementary roles in attentional function, as measured by the 5CSRTT. These functions are predominantly under the control of the prefrontal cortex and striatum. These conclusions are considered in the context of their application towards therapeutic approaches for attentional disturbances that are typically observed in schizophrenic patients.

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References

  • Altar CA, Wasley AM, Neale RF, Stone GA (1986) Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain. Brain Res Bull 16:517–525

    CAS  PubMed  Google Scholar 

  • Arnsten AF (1997) Catecholamine regulation of the prefrontal cortex. J Psychopharmacol 11:151–162

    Google Scholar 

  • Arnsten AF (2000) Through the looking glass: differential noradrenergic modulation of prefrontal cortical function. Neural Plast 7:133–146

    CAS  PubMed  Google Scholar 

  • Arnsten AF, Contant TA (1992) Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology 108:159–169

    CAS  PubMed  Google Scholar 

  • Baunez C, Robbins TW (1999) Effects of dopamine depletion of the dorsal striatum and further interaction with subthalamic nucleus lesions in an attentional task in the rat. Neuroscience 92:1343–1356

    CAS  PubMed  Google Scholar 

  • Baxter MG, Chiba AA (1999) Cognitive functions of the basal forebrain. Curr Opin Neurobiol 9:178–183

    CAS  PubMed  Google Scholar 

  • Birrell JM, Brown VJ (2000) Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20:4320–4324

    CAS  PubMed  Google Scholar 

  • Bourgin P, Huitron-Resendiz S, Spier AD, Fabre V, Morte B, Criado JR, Sutcliffe JG, Henriksen SJ, de Lecea L (2000) Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci 20:7760–7765

    CAS  PubMed  Google Scholar 

  • Blandina P, Giorgetti M, Bartolini L, Cecchi M, Timmerman H, Leurs R, Pepeu G, Giovannini MG (1996) Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats. Br J Pharmacol 119:1656–1664

    CAS  PubMed  Google Scholar 

  • Bleuler E (1950) Dementia praecox, or the group of schizophrenias (translated by J. Zinkin). International Universities Press, New York (original translation in 1911)

  • Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929–932

    CAS  PubMed  Google Scholar 

  • Burnham KE, Waters KA, O’Connor D, Dawson GR, Dias R (2003) Effects of modafinil on the rat five-choice serial reaction time test, a rodent model of attention. J Psychopharmacol 17:G46

    Google Scholar 

  • 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 9:361–380

    CAS  PubMed  Google Scholar 

  • Castner SA, Williams GV, Goldman-Rakic PS (2000) Reversal of anti-psychotic-induced working memory deficits by short term dopamine D1 receptor stimulation. Science 287:2020–2022

    Article  CAS  PubMed  Google Scholar 

  • Christakou A, Robbins TW, Everitt BJ (2001) Functional disconnection of a prefrontal cortical-dorsal striatal system disrupts choice reaction time performance: implications for attentional function. Behav Neurosci 115:812–825

    CAS  PubMed  Google Scholar 

  • Chudasama Y, Muir JL (2001) Visual attention in the rat: a role for the prelimbic cortex and thalamic nuclei? Behav Neurosci 115:417–428

    CAS  PubMed  Google Scholar 

  • Chudasama Y, Nathwani F, Robbins TW (2001) A novel task for assessing attention and working memory: neural and pharmacological validation. SFN abstract 533.10

    Google Scholar 

  • Chudasama Y, Passetti F, Rhodes SEV, Lopian D, Desai A, Robbins TW (2003) Dissociable aspects of performance on the five-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 146:105–119

    Article  CAS  PubMed  Google Scholar 

  • Cohen JD, Braver TS, O’Reilly RC (1999) A computational approach to prefrontal cortex: cognitive control and schizophrenia: recent developments and current challenge. In: AC Roberts, TW Robbins, L Weiskrantz (eds) The prefrontal cortex: executive and cognitive functions. Oxford University Press, New York, pp 195–220

  • 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 91:458–466

    CAS  PubMed  Google Scholar 

  • Cole BJ, Robbins TW (1989) Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi on performance of a 5-choice serial reaction time task in rats: implications for theories of selective attention and arousal. Behav Brain Res 33:165–179

    CAS  PubMed  Google Scholar 

  • Consolo S, Ramponi S, Ladinsky H, Baldi G (1996) A critical role for D1 receptors in the 5-HT1A-mediated facilitation of in vivo acetylcholine release in rat frontal cortex. Brain Res 707:320–323

    CAS  PubMed  Google Scholar 

  • Crofts HS, Dalley JW, Collins P, Van Denderen JCM, Everitt BJ, Robbins TW, Roberts AC (2001) Differential effects of 6-OHDA lesions of the prefrontal cortex and caudate nucleus on the ability to acquire an attentional set. Cereb Cortex 11:1015–1026

    Article  CAS  PubMed  Google Scholar 

  • Dalley JW, McGaughy J, O’Connell MT, Cardinal RN, Levita L, Robbins TW (2001) Distinct changes in cortical acetylcholine and noradrenaline efflux during contingent and noncontingent performance of a visual attentional task. J Neurosci 21:4908–4914

    CAS  Google Scholar 

  • Dalley JW, Theobald, DE, Pereira EAC, Li PMMC, Robbins TW (2002a) Specific abnormalities in serotonin release in the prefrontal cortex of isolation reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity. Psychopharmacology 164:329–340

    Article  CAS  PubMed  Google Scholar 

  • Dalley JW, Theobald DE, Eagle DM, Passetti F, Robbins TW (2002b) Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex. Neuropsychopharmacology 26:716–728

    CAS  PubMed  Google Scholar 

  • Davies DR, Parasuraman R (1982) The psychology of vigilance. Academic Press, London

  • Day J, Fibiger HC (1993) Dopaminergic regulation of cortical acetylcholine release: effects of dopamine receptor agonists. Neuroscience 54:643–648

    CAS  PubMed  Google Scholar 

  • Dias R, Robbins TW, Roberts AC (1996) Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav Neurosci 110:872–886

    Article  CAS  PubMed  Google Scholar 

  • Druzin MY, Kurzina NP, Malinina EP, Kozlov AP (2000) The effects of local application of D2 selective dopaminergic drugs into the medial prefrontal cortex of rats in a delayed spatial choice task. Behav Brain Res 109: 99–111

    Article  CAS  PubMed  Google Scholar 

  • Dustewitz D, Seamans JK, Sejnowski TJ (2000) Dopamine mediated stabilization of delay-period activity in a network model of prefrontal cortex. J Neurophysiol 83: 1733–1750

    CAS  PubMed  Google Scholar 

  • Epstein JI, Keefe RS, Roitman SL, Harvey PD, Mohs RC (1996) Impact of neuroleptic medications on continuous performance test measures in schizophrenia. Biol Psychiatry 39:902–905

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (1997) Central cholinergic systems and cognition. Annu Rev Psychol 48:649–684

    CAS  PubMed  Google Scholar 

  • Eysenck MW (1982) Attention and arousal, cognition and performance. Springer-Verlag, New York, pp 47–66

  • Ferraro L, Antonelli T, O’Connor WT, Tanganelli S, Rambert FA, Fuxe K (1997) Modafinil: an antinarcoleptic drug with a different neurochemical profile to d-amphetamine and dopamine uptake blockers. Biol Psychiatry 42:1181–1183

    CAS  PubMed  Google Scholar 

  • Florijn WJ, Tarazi FI, Creese I (1997) Dopamine receptor subtypes: differential regulation after 8 months treatment with antipsychotic drugs. J Pharmacol Exp Ther 280:561–569

    CAS  PubMed  Google Scholar 

  • 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 51:219–233

    Article  CAS  PubMed  Google Scholar 

  • 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 20:1208–1215

    PubMed  Google Scholar 

  • Grunder G, Carlsson A, Wong DF (2003) Mechanism of new antipsychotic medications: occupancy is not just antagonism. Arch Gen Psychiatry 60:974–977

    Article  PubMed  Google Scholar 

  • Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S, Benham CD, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Shah AS, Hatcher JP, Hatcher PD, Jones DN, Smith MI, Piper DC, Hunter AJ, Porter RA, Upton N (1999) Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci 96:10911–10916

    CAS  PubMed  Google Scholar 

  • Hahn B, Shoaib M, Stolerman IP (2002) Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands. Psychopharmacology 162:129–137

    CAS  PubMed  Google Scholar 

  • Hahn B, Shoaib M, Stolerman IP (2003) Involvement of the prefrontal cortex but not the dorsal hippocampus in the attention-enhancing effects of nicotine in rats. Psychopharmacology 168:271–279

    Article  CAS  PubMed  Google Scholar 

  • 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 133:329–342

    CAS  PubMed  Google Scholar 

  • Harvey PD, Napolitano JA, Mao L, Gharabawi G (2003) Comparative effects of risperidone and olanzapine on cognition in elderly patients with schizophrenia or schizoaffective disorder. Int J Geriatr Psychiatry 18:820–829

    Article  PubMed  Google Scholar 

  • an der Heiden W, Hafner H (2000) The epidemiology of onset and course of schizophrenia. Eur Arch Psychiatr Clin Neurosci 250:292–303

    Article  Google Scholar 

  • Higgins GA, Ballard TM, Huwyler J, Kemp JA, Gill R (2003) Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63–1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibition. Neuropharmacology 44:324–341

    Article  CAS  PubMed  Google Scholar 

  • Holland PC, Han JS, Gallagher M (2000) Lesions of the amygdala central nucleus alter performance on a selective attention task. J Neurosci 20:6701–6706

    CAS  PubMed  Google Scholar 

  • Hori T, Subramaniam S, Srivastava LK, Quirion R (2000) Behavioral and neurochemical alterations following repeated phencyclidine administration in rats with neonatal ventral hippocampal lesions. Neuropharmacology 39:2478–2491

    Article  CAS  PubMed  Google Scholar 

  • Humby T, Laird FM, Davies W, Wilkinson LS (1999) Visuospatial attentional functioning in mice: interactions between cholinergic manipulations and genotype. Eur J Neurosci 11:2813–2823

    CAS  PubMed  Google Scholar 

  • Ichikawa J, Dai J, Meltzer HY (2002) 5-HT1A and 5-HT2A receptors minimally contribute to clozapine-induced acetylcholine release in rat medial prefrontal cortex. Brain Res 939:34–42

    PubMed  Google Scholar 

  • Ivanov A, Aston-Jones G (2000) Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons. Neuroreport 11:1755–1758

    CAS  PubMed  Google Scholar 

  • Iversen LL (1975) Dopamine receptors in the brain. Science 188:1084–1089

    CAS  PubMed  Google Scholar 

  • Iversen LL (1985) Mechanism of action of antipsychotic drugs: retrospect and prospect. In: Iversen SD (ed) Psychopharmacology: recent advances and future prospects. Oxford University Press, New York, pp 204–215

  • Iwamoto ET (1984) An assessment of the spontaneous activity of rats administered morphine, phencyclidine, or nicotine using automated and observational methods. Psychopharmacology 84:374–382

    CAS  PubMed  Google Scholar 

  • Jacobs PS, Taylor BM, Bardgett ME (2000) Maturation of locomotor and Fos responses to the NMDA antagonists, PCP and MK-801. Dev Brain Res 122:91–95

    Article  CAS  Google Scholar 

  • Jin J, Yamamoto T, Watanabe S (1997) The involvement of sigma receptors in the choice reaction performance deficits induced by phencyclidine. Eur J Pharmacol 319:147–152

    Article  CAS  PubMed  Google Scholar 

  • Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA (1992) Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer’s disease. Psychopharmacology 108:485–494

    CAS  PubMed  Google Scholar 

  • Jones P, Rodgers B, Murray R, Marmot M (1994) Child development risk factors for adult schizophrenia in the British birth cohort. Lancet 344:1398–1402

    CAS  PubMed  Google Scholar 

  • Kato K, Shishido T, Ono M, Shishido K, Kobayashi M, Suzuki H, Nabeshima T, Furukawa H, Niwa S (2000) Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats. Psychopharmacology 150:163–169

    Article  CAS  PubMed  Google Scholar 

  • Keefe RS, Silverman JM, Mohs RC, Siever LJ, Harvey PD, Friedman L, Roitman SE, DuPre RL, Smith CJ, Schmeidler J, Davis KL (1997) Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. Arch Gen Psychiatry 54:169–176

    CAS  PubMed  Google Scholar 

  • Kirkby DL, Higgins GA (1998) Characterization of perforant path lesions in rodent models of memory and attention. Eur J Neurosci 10:823–838

    CAS  PubMed  Google Scholar 

  • Koelega HS (1993) Stimulant drugs and vigilance performance: a review (1993) Psychopharmacology 111:1–16

    CAS  PubMed  Google Scholar 

  • Kornetsky C, Mirsky AF (1966) On certain psychopharmacological and physiological differences between schizophrenics and normal persons, Psychopharmacologia 8:309–318

    Google Scholar 

  • Koskinen T, Sirvio J (2001) Studies on the involvement of the dopaminergic system in the 5-HT2 agonist (DOI)-induced premature responding in a five-choice serial reaction time task. Brain Res Bull 54:65–75

    CAS  PubMed  Google Scholar 

  • Koskinen T, Ruotsalainen S, Puumala T, Lappalainen R, Koivisto E, Mannisto PT, Sirvio J (2000) Activation of 5-HT2A receptors impairs response control of rats in a five-choice serial reaction time task. Neuropharmacology 39:471–481

    CAS  PubMed  Google Scholar 

  • Kraepelin E (1971) Dementia praecox (translated by Barclay E, Barclay S) Churchill Livingstone, New York (original work published in 1919)

  • Kuroki T, Meltzer HY, Ichikawa J (1999) Effects of antipsychotic drugs on extracellular opamine levels in rat medial prefrontal cortex and nucleus accumbens. Pharmacol Exp Ther 288:774–781

    CAS  PubMed  Google Scholar 

  • Lehmann O, Grottick AJ, Cassel J-C, Higgins GA (2001) 192 IgG saporin-induced lesions of the basal forebrain: effects on attention as assessed by the 5-choice serial reaction time task. Behav Pharmacol 12:S58

    Google Scholar 

  • Le Pen G, Grottick AJ, Higgins GA, Moreau JL (2003) Phencyclidine exacerbates attentional deficits in a neurodevelopmental rat model of schizophrenia. Neuropsychopharmacology 28:1799–1809

    Article  PubMed  Google Scholar 

  • Leucht S, Pitschel-Walz G, Abraham D, Kissling W (1999) Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 35:51–68

    CAS  PubMed  Google Scholar 

  • Leurs R, Blandina P, Tedford C, Timmerman H (1998) Therapeutic potential of histamine H3 receptor agonists and antagonists. Trends Pharmacol Sci 19:177-183

    CAS  PubMed  Google Scholar 

  • Lidow MS, Goldman-Rakic PS (1994) A common action of clozapine, haloperidol, and remoxipride on D1- and D2-dopaminergic receptors in the primate cerebral cortex. Proc Natl Acad Sci USA 91:4353–4356

    CAS  PubMed  Google Scholar 

  • Lidow MS, Elsworth JD, Goldman-Rakic PS (1997) Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs. J Pharmacol Exp Ther 281:597–603

    CAS  PubMed  Google Scholar 

  • Lidow MS, Williams GV, Goldman-Rakic PS (1998) The cerebral cortex: a case for a common site of action of antipsychotics. Trends Pharmacol Sci 19:136–140

    CAS  Google Scholar 

  • Ligneau X, Lin J, Vanni-Mercier G, Jouvet M, Muir JL, Ganellin CR, Stark H, Elz S, Schunack W, Schwartz J (1998) Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist. J Pharmacol Exp Ther 287:658–666

    CAS  PubMed  Google Scholar 

  • Lin JS, Sakai K, Vanni-Mercier G, Jouvet M (1989) A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res 479:225–240

    Article  CAS  PubMed  Google Scholar 

  • Lin JS, Hou Y, Jouvet M (1996) Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc Natl Acad Sci 93:14128–14133

    CAS  PubMed  Google Scholar 

  • McGaughy J, Sarter M (1995) Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands. Psychopharmacology 117:340-357

    CAS  PubMed  Google Scholar 

  • McGaughy J, Turchi J, Sarter M (1994) Crossmodal divided attention in rats: effects of chlordiazepoxide and scopolamine. Psychopharmacology 115:213–220

    CAS  PubMed  Google Scholar 

  • McGaughy J, Dalley JW, Morrison CH, Everitt BJ, Robbins TW (2002) Selective behavioral and neurochemical effects of cholinergic lesions produced by intrabasalis infusions of 192 IgG-saporin on attentional performance in a five-choice serial reaction time task. J Neurosci 22:1905–1913

    CAS  PubMed  Google Scholar 

  • Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99:S18–27

    PubMed  Google Scholar 

  • Meltzer HY (1999) The role of serotonin in antipsychotic drug action. Neuropsychopharmacology 21:106S–115S

    CAS  PubMed  Google Scholar 

  • Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr 25:233–255

    CAS  PubMed  Google Scholar 

  • Meltzer HY, Matsubara S, Lee JC (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther 251:238–246

    CAS  PubMed  Google Scholar 

  • Millan MJ (2000) Improving the treatment of schizophrenia: focus on serotonin 5-HT1A receptors. J Pharmacol Exp Ther 295:853–861

    CAS  PubMed  Google Scholar 

  • Milstein JA, Dalley JW, Theobald DEH, Robbins TW (2003) Effect of modafinil on performance of the 5-choice serial reaction time task in rats. J Psychopharmacol 17:G45

    Google Scholar 

  • Miner L AH, Ostrander M, Sarter M (1997) Effects of ibotenic acid-induced loss of neurons in the medial prefrontal cortex of rats on behavioral vigilance: evidence for executive dysfunction. J Psychopharmacol 11:169–178

    CAS  PubMed  Google Scholar 

  • Mirza NR, Stolerman IP (2000) The role of nicotinic and muscarinic acetylcholine receptors in attention. Psychopharmacology 148:243–250

    CAS  PubMed  Google Scholar 

  • Moghaddam B, Bunney BS (1990) Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study. J Neurochem 54:1755–1760

    CAS  PubMed  Google Scholar 

  • Muir JL (1996) Attention and stimulus processing in the rat. Cognit Brain Res 3:215–225

    CAS  Google Scholar 

  • Muir JL, Robbins TW, Everitt BJ (1992) Disruptive effects of muscimol infused into the basal forebrain on conditional discrimination and visual attention: differential interactions with cholinergic mechanisms. Psychopharmacology 107:541–550

    CAS  PubMed  Google Scholar 

  • 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 14:2313–2326

    CAS  PubMed  Google Scholar 

  • Muir JL, Everitt BJ, Robbins TW (1995) Reversal of visual attentional dysfunction following lesions of the cholinergic basal forebrain by physostigmine and nicotine but not by the 5-HT3 receptor antagonist, ondansetron. Psychopharmacology 118:82–92

    CAS  PubMed  Google Scholar 

  • Muir JL, Everitt BJ, Robbins TW (1996a). 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 6:470–481

    CAS  PubMed  Google Scholar 

  • Muir JL, Bussey TJ, Everitt BJ, Robbins TW (1996b) Dissociable effects of AMPA-induced lesions of the vertical limb diagonal band of Broca on performance of the 5-choice serial reaction time task and on acquisition of a conditional visual discrimination. Behav Brain Res 82:31–44

    CAS  PubMed  Google Scholar 

  • Murray TF, Horita A (1979) Phencyclidine-induced stereotyped behavior in rats: dose response effects and antagonism by neuroleptics. Life Sci 24:2217–2225

    Article  CAS  PubMed  Google Scholar 

  • Neil W, Curran S, Wattis J (2003) Antipsychotic prescribing in older people. Age Ageing 32:475–483

    Article  PubMed  Google Scholar 

  • Nestor PG, O’Donnell BF (1998) The mind adrift: attentional dysregulation in schizophrenia. In: Parasuraman R (eds) The attentive brain. MIT Press, Cambridge, Mass., pp 527–546

  • Nestor PG, Faux S, McCarley RW, Shenton ME, Sands SF (1990) Measurement of visual sustained attention in schizophrenia using signal detection analysis and a newly developed computerized CPT. Schizophr Res 3:329–332

    Article  CAS  PubMed  Google Scholar 

  • Nieuwenstein MR, Aleman A, de Haan EH (2003) Relationship between symptom dimensions and neurocognitive functioning in schizophrenia: a meta-analysis of WCST and CPT studies. Wisconsin Card Sorting Test. Continuous Performance Test. J Psychiatr Res 35:119–125

    Article  Google Scholar 

  • Nuechterlein KH, Dawson ME (1984) Information processing and attentional functioning in the developmental course of schizophrenic disorders. Schizophr Bull 10:160-203

    CAS  PubMed  Google Scholar 

  • Nuechterlein KH, Parasuraman R, Qiyuan J (1983) Visual sustained attention: image degradation produces rapid sensitivity decrements over time. Science 220:327–329

    CAS  PubMed  Google Scholar 

  • Orzack MH, Kornetsky C, Freeman H (1967) The effects of daily carphenazine on attention in the schizophrenic patient. Psychopharmacologia 11:31–38

    CAS  PubMed  Google Scholar 

  • Pantelis C, Barber EZ, Barnes TRE, Nelson HE, Owen AM, Robbins TW (1999) A comparison of set-shifting ability in patients with schizophrenia and frontal lobe damage. Schizophr Res 37:251–270

    CAS  PubMed  Google Scholar 

  • Parasuraman R (1998) The attentive brain: issues and concepts. In: Parasuraman R (ed) The attentive brain. MIT Press, Cambridge, Mass., pp 3–15

  • Parasuraman R, Davis DR (1977). A taxonomic analysis of vigilance. In: Mackie RR (eds) Vigilance, theory, operational performance and physiological correlates Plenum Press, New York

  • Passetti F, Dalley JW, O’Connell MT, Everitt BJ, Robbins TW (2000) Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task. Eur J Neurosci 12:3051–3058

    CAS  PubMed  Google Scholar 

  • Passetti F, Chudasama Y, Robbins TW (2002) The frontal cortex of the rat and visual attentional performance: dissociable functions of distinct medial prefrontal subregions. Cereb Cortex 12:1254–68

    Article  PubMed  Google Scholar 

  • Passetti F, Levita L, Robbins TW (2003) Sulpiride alleviates the attentional impairments of rats with medial prefrontal cortex lesions. Behav Brain Res 138:59–69

    Article  CAS  PubMed  Google Scholar 

  • Pollard H, Moreau J, Arrang JM, Schwartz JC (1993) A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas. Neuroscience 52:169–189

    CAS  PubMed  Google Scholar 

  • 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 66:198–211

    Article  CAS  PubMed  Google Scholar 

  • Puumala T, Riekkinen P Sr, Sirvio J (1997) Modulation of vigilance and behavioral activation by alpha-1 adrenoceptors in the rat. Pharmacol Biochem Behav 56:705–712

    CAS  PubMed  Google Scholar 

  • Rang HP, Dale MM, Ritter JM (1995) Pharmacology, 3rd edn. Churchill Livingstone, New York

  • Robbins TW (1997) Arousal systems and attentional processes. Biol Psychol 45:57–71

    CAS  PubMed  Google Scholar 

  • Robbins TW (1998) Arousal and attention: Psychopharmacological and neuropsychological studies in experimental animals. In: Parasuraman R (ed) The attentive brain. MIT Press, Cambridge, Mass., pp 189–220

  • Robbins TW (2000) Chemical neuromodulation of frontal-executive functions in humans and other animals. Exp Brain Res 133:130–138.

    CAS  PubMed  Google Scholar 

  • Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163:362–380

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW, Everitt BJ (1995a) Arousal systems and attention. In: Gazzinga M (ed) The cognitive neurosciences. MIT Press, Cambridge Mass., pp 703–725

  • Robbins TW, Everitt BJ (1995b) Central norepinephrine neurons and behaviour. In: Bloom FE, Kupfer D (eds) Psychopharmacology, 4th generation of progress. Raven Press, New York, pp 363–372

  • Robbins TW, Muir JL, Killcross AS, Pretsell D (1993) Methods for assessing attention and stimulus control in the rat. In: Sahgal A (ed) Behavioural neuroscience: a practical approach, vol 1. Oxford University Press, New York, pp 13–47

  • Robbins TW, Granon S, Muir JL, Durantou F, Harrison A, Everitt BJ (1998) Neural systems underlying arousal and attention. Implications for drug abuse. Ann N Y Acad Sci 846:222–237

    CAS  PubMed  Google Scholar 

  • Rosvold HE, Mirsky AF, Sarason I, Bransome EB, Beck LH (1956) A continuous performance test of brain damage. J Consult Psychology 20:343–350

    Google Scholar 

  • Rush CR, Kelly TH, Hays LR, Baker RW, Wooten AF (2002) Acute behavioral and physiological effects of modafinil in drug abusers. Behav Pharmacol 13:105–115

    CAS  PubMed  Google Scholar 

  • Sahakian BJ, Sarna GS, Kantamaneni BD, Jackson A, Hutson PH, Curzon G (1985) Association between learning and cortical catecholamines in non-drug-treated rats. Psychopharmacology 86:339–343

    Google Scholar 

  • Sahakian BJ, Jones GM, Levy R, Gray JA, Warburton DM (1989) The effects of nicotine on attention, information processing and short-term memory in patients with dementia of the Alzheimer’s type. Br J Psychiatry 154:797–800

    CAS  PubMed  Google Scholar 

  • Sahakian BJ, Owen AM, Morant NJ, Eagger SA, Boddington S, Crayton L, Crockford HA, Crooks M, Hill K, Levy R (1993) Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer’s disease: assessment of attentional and mnemonic function using CANTAB. Psychopharmacology 110:395–401

    CAS  PubMed  Google Scholar 

  • Sarter M (1994) Neuronal mechanisms of the attentional dysfunctions in senile dementia and schizophrenia: two sides of the same coin? Psychopharmacology 114:539–550

    CAS  PubMed  Google Scholar 

  • Sarter M, Bruno JP (1997) Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Res Rev 23:28–46

    CAS  PubMed  Google Scholar 

  • Sarter M, Bruno JP (2000) Cortical cholinergic inputs mediating arousal, attentional processing and dreaming: differential afferent regulation of the basal forebrain by telencephalic and brainstem afferents. Neuroscience 95:933–952

    CAS  PubMed  Google Scholar 

  • Sawaguchi T, Goldman-Rakic PS (1991) D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251:947–950

    CAS  PubMed  Google Scholar 

  • Schwartz JC, Arrang JM, Garbarg M, Traiffort E (1995) Histamine. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation of progress. Raven Press, New York, pp 397–405

  • Seamans JK, Floresco SB, Phillips AG (1998) D1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat. J Neurosci 18:1613–1621

    CAS  PubMed  Google Scholar 

  • Steele TD, Hodges DB Jr, Levesque TR, Locke KW (1997) D1 agonist dihydrexidine releases acetylcholine and improves cognitive performance in rats. Pharmacol Biochem Behav 58:477–483

    Google Scholar 

  • Sirvio J, Jakala P, Mazurkiewicz M, Haapalinna A, Riekkinen P Jr, Riekkinen PJ (1993) Dose- and parameter-dependent effects of atipamezole, an alpha 2-antagonist, on the performance of rats in a five-choice serial reaction time task. Pharmacol Biochem Behav 45:123–129

    CAS  PubMed  Google Scholar 

  • Sirvio J, Mazurkiewicz M, Haapalinna A, Riekkinen P Jr, Lahtinen H, Riekkinen PJ Sr (1994) The effects of selective alpha-2 adrenergic agents on the performance of rats in a 5-choice serial reaction time task. Brain Res Bull 35:451–455

    CAS  PubMed  Google Scholar 

  • Steinpreis RE (1996) The behavioral and neurochemical effects of phencyclidine in humans and animals: some implications for modelling psychosis. Behav Brain Res 74:45–55

    CAS  PubMed  Google Scholar 

  • Stolerman IP, Mirza NR, Shoaib M (1995) Nicotine psychopharmacology: addiction, cognition and neuroadaptation. Med Res Rev15:47–72

    Google Scholar 

  • Stolerman IP, Mirza NR, Hahn B, Shoaib M (2000) Nicotine in an animal model of attention. Eur J Pharmacol 393:147–154

    CAS  PubMed  Google Scholar 

  • Tamminga CA, Carlsson A (2002) Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Curr Drug Target CNS Neurol Disord 1:141–147

    CAS  PubMed  Google Scholar 

  • Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003) Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology 165:260–269

    CAS  PubMed  Google Scholar 

  • Usher M, Cohen JD, Servan-Schreiber D, Rajkowski J, Aston-Jones G (1999) The role of locus coeruleus in the regulation of cognitive performance. Science 283:549–554

    Article  CAS  PubMed  Google Scholar 

  • Verebey K, Kogan MJ, Mule SJ (1981) Phencyclidine-induced stereotype in rats: effects of methadone, apomorphine, and naloxone. Psychopharmacology 75:44–47

    CAS  PubMed  Google Scholar 

  • Weed MR, Gold LH (1998) The effects of dopaminergic agents on reaction time in rhesus monkeys. Psychopharmacology 137:33–42

    Article  CAS  PubMed  Google Scholar 

  • Wesnes K, Warburton DM (1984) Effects of scopolamine and nicotine on human rapid information processing. Psychopharmacology 82:147–150

    CAS  PubMed  Google Scholar 

  • Wiley RG, Oeltmann TN, Lappi DA (1991) Immunolesioning: selective destruction of neurons using immunotoxin to rat NGF receptor. Brain Res 562:149–153

    CAS  PubMed  Google Scholar 

  • Wilkinson LS, Killcross AS, Humby T, Hall FS, Geyer MA, Robbins TW (1994) Social isolation produces developmentally-specific deficits in pre-pulse inhibition of the acoustic startle response but does not disrupt latent inhibition. Neuropsychopharmacology 10:61–72

    Google Scholar 

  • Wilkinson RT (1963) Interaction of noise with knowledge of results and sleep deprivation. J Exp Psychol 66:332–337

    CAS  Google Scholar 

  • Winstanley CA, Chudasama Y, Dalley JW, Theobald DE, Glennon JC, Robbins TW (2003) Intra-prefrontal 8-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats. Psychopharmacology 167:304–314

    CAS  PubMed  Google Scholar 

  • Wohlberg GW, Kornetsky C (1973) Sustained attention in remitted schizophrenics. Arch Gen Psychiatry 28:533–537

    CAS  PubMed  Google Scholar 

  • Zahrt J, Taylor JR, Mathew RG, Arnsten AF (1997) Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci 17:8528–8535

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. National Institute of Mental Health, Building 49, Room 1B80, Convent Drive, Bethesda, MD 20892, USA

    Y. Chudasama

  2. Cambridge University, Department of Experimental Psychology, Downing Street, Cambridge, CB2 3EB, UK

    T. W. Robbins

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  1. Y. Chudasama
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Correspondence to Y. Chudasama.

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Chudasama, Y., Robbins, T.W. Psychopharmacological approaches to modulating attention in the five-choice serial reaction time task: implications for schizophrenia. Psychopharmacology 174, 86–98 (2004). https://doi.org/10.1007/s00213-004-1805-y

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