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Behavioral Animal Models to Assess Pro-cognitive Treatments for Schizophrenia

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Novel Antischizophrenia Treatments

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 213))

Abstract

Cognitive dysfunction is a core aspect of schizophrenia that constitutes a major obstacle toward reintegration of patients into society. Although multiple cognitive deficits are evident in schizophrenia patients, no medication is currently approved for their amelioration. Although consensus clinical test batteries have been developed for the assessment of putative cognition enhancers in patients with schizophrenia, parallel animal tests remain to be validated. Having no approved treatment for cognitive symptoms means no positive control can be used to examine pharmacological predictive validity of animal models. Thus, focus has been placed on animal paradigms that have demonstrable construct validity for the cognitive domain being assessed.

This review describes the growing arsenal of animal paradigms under development that have putative construct validity to cognitive domains affected in schizophrenia. We discuss (1) the construct validity of the paradigms; (2) compounds developed to investigate putative treatment targets; and (3) manipulations used to first impair task performance. Focus is placed on the paradigm design, including how the use of multivariate assessments can provide evidence that main effects of treatment are not confounded by extraneous effects.

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References

  • Abdul-Monim Z, Reynolds GP, Neill JC (2003) The atypical antipsychotic ziprasidone, but not haloperidol, improves phencyclidine-induced cognitive deficits in a reversal learning task in the rat. J Psychopharmacol 17:57–65

    Article  PubMed  CAS  Google Scholar 

  • Abdul-Monim Z, Reynolds GP, Neill JC (2006) The effect of atypical and classical antipsychotics on sub-chronic PCP-induced cognitive deficits in a reversal-learning paradigm. Behav Brain Res 169:263–273

    Article  PubMed  CAS  Google Scholar 

  • Abraham NM, Spors H, Carleton A, Margrie TW, Kuner T, Schaefer AT (2004) Maintaining accuracy at the expense of speed: stimulus similarity defines odor discrimination time in mice. Neuron 44:865–876

    PubMed  CAS  Google Scholar 

  • Addy NA, Nakijama A, Levin ED (2003) Nicotinic mechanisms of memory: effects of acute local DHbetaE and MLA infusions in the basolateral amygdala. Brain Res Cogn Brain Res 16:51–57

    Article  PubMed  CAS  Google Scholar 

  • Amitai N, Markou A (2009) Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration. Psychopharmacology (Berl) 202:275–286

    Article  CAS  Google Scholar 

  • Amitai N, Semenova S, Markou A (2007) Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation by atypical antipsychotic medications in rats. Psychopharmacology (Berl) 193:521–537

    Article  CAS  Google Scholar 

  • Ammassari-Teule M, Save E, de Marsanich B, Thinus-Blanc C (1998) Posterior parietal cortex lesions severely disrupt spatial learning in DBA mice characterized by a genetic hippocampal dysfunction. Behav Brain Res 95:85–90

    Article  PubMed  CAS  Google Scholar 

  • Antonova E, Parslow D, Brammer M, Simmons A, Williams S, Dawson GR, Morris RG (2010) Scopolamine disrupts hippocampal activity during allocentric spatial memory in humans: an fMRI study using a virtual reality analogue of the Morris Water Maze. J Psychopharmacol 25(9):1256–65

    Article  PubMed  CAS  Google Scholar 

  • Arnsten AF (2004) Adrenergic targets for the treatment of cognitive deficits in schizophrenia. Psychopharmacology (Berl) 174:25–31

    Article  CAS  Google Scholar 

  • Aron AR, Poldrack RA (2005) The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1285–1292

    Article  PubMed  Google Scholar 

  • Baddeley A (2001) The concept of episodic memory. Philos Trans R Soc Lond B Biol Sci 356:1345–1350

    Article  PubMed  CAS  Google Scholar 

  • Baddeley AD (1986) Working memory. Oxford University Press, Oxford

    Google Scholar 

  • Balducci C, Nurra M, Pietropoli A, Samanin R, Carli M (2003) Reversal of visual attention dysfunction after AMPA lesions of the nucleus basalis magnocellularis (NBM) by the cholinesterase inhibitor donepezil and by a 5-HT1A receptor antagonist WAY 100635. Psychopharmacology (Berl) 167:28–36

    CAS  Google Scholar 

  • Bancroft A, Levin ED (2000) Ventral hippocampal alpha4beta2 nicotinic receptors and chronic nicotine effects on memory. Neuropharmacology 39:2770–2778

    Article  PubMed  CAS  Google Scholar 

  • Barch DM, Carter CS, Arnsten A, Buchanan RW, Cohen JD, Geyer M, Green MF, Krystal JH, Nuechterlein K, Robbins T, Silverstein S, Smith EE, Strauss M, Wykes T, Heinssen R (2009) Selecting paradigms from cognitive neuroscience for translation into use in clinical trials: proceedings of the third CNTRICS meeting. Schizophr Bull 35:109–114

    Article  PubMed  Google Scholar 

  • Barense MD, Fox MT, Baxter MG (2002) Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats. Learn Mem 9:191–201

    Article  PubMed  Google Scholar 

  • Barnes SA, Young JW, Neill JC (2011a) D(1) receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test. Psychopharmacology (Berl) 220(1):129–41

    Article  CAS  Google Scholar 

  • Barnes SA, Young JW, Neill JC (2011b) Rats tested after a washout period from sub-chronic PCP administration exhibited impaired performance in the 5-Choice Continuous Performance Test (5C-CPT) when the attentional load was increased. Neuropharmacology 62(3):1432–41

    Article  PubMed  CAS  Google Scholar 

  • Barnett JH, Robbins TW, Leeson VC, Sahakian BJ, Joyce EM, Blackwell AD (2010) Assessing cognitive function in clinical trials of schizophrenia. Neurosci Biobehav Rev 34:1161–1177

    Article  PubMed  Google Scholar 

  • Benice TS, Raber J (2009) Dihydrotestosterone modulates spatial working-memory performance in male mice. J Neurochem 110:902–911

    Article  PubMed  CAS  Google Scholar 

  • Berg EA (1948) A simple objective technique for measuring flexibility in thinking. J Gen Psychol 39:15–22

    Article  PubMed  CAS  Google Scholar 

  • Bettany JH, Levin ED (2001) Ventral hippocampal alpha 7 nicotinic receptor blockade and chronic nicotine effects on memory performance in the radial-arm maze. Pharmacol Biochem Behav 70:467–474

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Bissonette GB, Martins GJ, Franz TM, Harper ES, Schoenbaum G, Powell EM (2008) Double dissociation of the effects of medial and orbital prefrontal cortical lesions on attentional and affective shifts in mice. J Neurosci 28:11124–11130

    Article  PubMed  CAS  Google Scholar 

  • Blokland A (1998) Reaction time responding in rats. Neurosci Biobehav Rev 22:847–864

    Article  PubMed  CAS  Google Scholar 

  • Bodyak N, Slotnick B (1999) Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory. Chem Senses 24:637–645

    Article  PubMed  CAS  Google Scholar 

  • Bor D, Duncan J, Owen AM (2001) The role of spatial configuration in tests of working memory explored with functional neuroimaging. Scand J Psychol 42:217–224

    Article  PubMed  CAS  Google Scholar 

  • Bor D, Owen AM (2006) Working memory: linking capacity with selectivity. Curr Biol 16:R136–R138

    Article  PubMed  CAS  Google Scholar 

  • Bozikas VP, Kosmidis MH, Kiosseoglou G, Karavatos A (2006) Neuropsychological profile of cognitively impaired patients with schizophrenia. Compr Psychiatry 47:136–143

    Article  PubMed  Google Scholar 

  • Brigman JL, Bussey TJ, Saksida LM, Rothblat LA (2005) Discrimination of multidimensional visual stimuli by mice: intra- and extradimensional shifts. Behav Neurosci 119:839–842

    Article  PubMed  Google Scholar 

  • Bromley-Brits K, Deng Y, Song W (2011) Morris water maze test for learning and memory deficits in Alzheimer’s disease model mice. J Vis Exp 53. pii: 2920. doi:10.3791/2920

    Google Scholar 

  • Buchanan RW, Conley RR, Dickinson D, Ball MP, Feldman S, Gold JM, McMahon RP (2007a) Galantamine for the Treatment of Cognitive Impairments in People With Schizophrenia. Am J Psychiatry 165(1):82–9

    Google Scholar 

  • Buchanan RW, Davis M, Goff D, Green MF, Keefe RS, Leon AC, Nuechterlein KH, Laughren T, Levin R, Stover E, Fenton W, Marder SR (2005) A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull 31:5–19

    Article  PubMed  Google Scholar 

  • Buchanan RW, Freedman R, Javitt DC, Abi-Dargham A, Lieberman JA (2007b) Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophr Bull 33:1120–1130

    Article  PubMed  Google Scholar 

  • Burk JA (2004) Introduction of a retention interval in a sustained attention task in rats: effects of a visual distracter and increasing the inter-trial interval. Behav Processes 67:521–531

    Article  PubMed  Google Scholar 

  • Bushnell PJ (1998) Behavioral approaches to the assessment of attention in animals. Psychopharmacology (Berl) 138:231–259

    Article  CAS  Google Scholar 

  • Bushnell PJ, Kelly KL, Crofton KM (1994) Effects of toluene inhalation on detection of auditory signals in rats. Neurotoxicol Teratol 16:149–160

    Article  PubMed  CAS  Google Scholar 

  • Bushnell PJ, Oshiro WM, Padnos BK (1997) Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention. Psychopharmacology (Berl) 134:230–241

    Article  CAS  Google Scholar 

  • Bussey TJ, Holmes A, Lyon L, Mar AC, McAllister KA, Nithianantharajah J, Oomen CA, Saksida LM (2011) New translational assays for preclinical modelling of cognition in schizophrenia: The touchscreen testing method for mice and rats. Neuropharmacology 62(3):1191–203

    Article  PubMed  CAS  Google Scholar 

  • Caine SB, Negus SS, Mello NK (1999) Method for training operant responding and evaluating cocaine self-administration behavior in mutant mice. Psychopharmacology (Berl) 147:22–24

    Article  CAS  Google Scholar 

  • Calcagno E, Carli M, Baviera M, Invernizzi RW (2009) Endogenous serotonin and serotonin2C receptors are involved in the ability of M100907 to suppress cortical glutamate release induced by NMDA receptor blockade. J Neurochem 108:521–532

    Article  PubMed  CAS  Google Scholar 

  • Carli M, Baviera M, Invernizzi RW, Balducci C (2006) Dissociable contribution of 5-HT1A and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. Neuropsychopharmacology 31:757–767

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • Carrozzo M, Koch G, Turriziani P, Caltagirone C, Carlesimo GA, Lacquaniti F (2005) Integration of cognitive allocentric information in visuospatial short-term memory through the hippocampus. Hippocampus 15:1072–1084

    Article  PubMed  CAS  Google Scholar 

  • Carter CS, Barch DM (2007) Cognitive neuroscience-based approaches to measuring and improving treatment effects on cognition in schizophrenia: the CNTRICS initiative. Schizophr Bull 33:1131–1137

    Article  PubMed  Google Scholar 

  • Cassens G, Inglis AK, Appelbaum PS, Gutheil TG (1990) Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophr Bull 16:477–499

    Article  PubMed  CAS  Google Scholar 

  • Cave CB, Squire LR (1992) Intact verbal and nonverbal short-term memory following damage to the human hippocampus. Hippocampus 2:151–163

    Article  PubMed  CAS  Google Scholar 

  • Chen WJ, Faraone SV (2000) Sustained attention deficits as markers of genetic susceptibility to schizophrenia. Am J Med Genet 97:52–57

    Article  PubMed  CAS  Google Scholar 

  • Chouinard S, Sepehry AA, Stip E (2007) Oral cholinesterase inhibitor add-on therapy for cognitive enhancement in schizophrenia: a quantitative systematic review, Part I. Clin Neuropharmacol 30:169–182

    Article  PubMed  CAS  Google Scholar 

  • Chudasama Y, Passetti F, Rhodes SE, Lopian D, Desai A, Robbins TW (2003) Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav Brain Res 146(1–2):105–119

    Article  PubMed  CAS  Google Scholar 

  • Chudasama Y, Robbins TW (2004) Psychopharmacological approaches to modulating attention in the five-choice serial reaction time task: implications for schizophrenia. Psychopharmacology (Berl) 174:86–98

    Article  CAS  Google Scholar 

  • Chuhan YS, Taukulis HK (2006) Impairment of single-trial memory formation by oral methylphenidate in the rat. Neurobiol Learn Mem 85:125–131

    Article  PubMed  CAS  Google Scholar 

  • Cornblatt B, Obuchowski M, Schnur D, O’Brien JD (1998) Hillside study of risk and early detection in schizophrenia. Br J Psychiatry Suppl 172:26–32

    PubMed  CAS  Google Scholar 

  • Cornblatt B, Obuchowski M, Schnur DB, O’Brien JD (1997) Attention and clinical symptoms in schizophrenia. Psychiatr Q 68:343–359

    Article  PubMed  CAS  Google Scholar 

  • Cornblatt BA, Keilp JG (1994) Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull 20:31–46

    Article  PubMed  CAS  Google Scholar 

  • Cornblatt BA, Malhotra AK (2001) Impaired attention as an endophenotype for molecular genetic studies of schizophrenia. Am J Med Genet 105:11–15

    Article  PubMed  CAS  Google Scholar 

  • Curtis CE (2006) Prefrontal and parietal contributions to spatial working memory. Neuroscience 139:173–180

    Article  PubMed  CAS  Google Scholar 

  • D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36:60–90

    Article  PubMed  Google Scholar 

  • Deller T, Sarter M (1998) Effects of repeated administration of amphetamine on behavioral vigilance: evidence for "sensitized" attentional impairments. Psychopharmacology (Berl) 137:410–414

    Article  CAS  Google Scholar 

  • Demeter E, Sarter M, Lustig C (2008) Rats and humans paying attention: cross-species task development for translational research. Neuropsychology 22:787–799

    Article  PubMed  Google Scholar 

  • Dere E, Zheng-Fischhofer Q, Viggiano D, Gironi Carnevale UA, Ruocco LA, Zlomuzica A, Schnichels M, Willecke K, Huston JP, Sadile AG (2008) Connexin31.1 deficiency in the mouse impairs object memory and modulates open-field exploration, acetylcholine esterase levels in the striatum, and cAMP response element-binding protein levels in the striatum and piriform cortex. Neuroscience 153:396–405

    Article  PubMed  CAS  Google Scholar 

  • DeVito LM, Konigsberg R, Lykken C, Sauvage M, Young WS 3rd, Eichenbaum H (2009) Vasopressin 1b receptor knock-out impairs memory for temporal order. J Neurosci 29:2676–2683

    Article  PubMed  CAS  Google Scholar 

  • DeVito LM, Lykken C, Kanter BR, Eichenbaum H (2010) Prefrontal cortex: role in acquisition of overlapping associations and transitive inference. Learn Mem 17:161–167

    Article  PubMed  Google Scholar 

  • Didriksen M, Kreilgaard M, Arnt J (2006) Sertindole, in contrast to clozapine and olanzapine, does not disrupt water maze performance after acute or chronic treatment. Eur J Pharmacol 542:108–115

    Article  PubMed  CAS  Google Scholar 

  • Drew LJ, Stark KL, Fenelon K, Karayiorgou M, Macdermott AB, Gogos JA (2011) Evidence for altered hippocampal function in a mouse model of the human 22q11.2 microdeletion. Mol Cell Neurosci 47:293–305

    Article  PubMed  CAS  Google Scholar 

  • Dudchenko PA (2004) An overview of the tasks used to test working memory in rodents. Neurosci Biobehav Rev 28:699–709

    Article  PubMed  Google Scholar 

  • Dudchenko PA, Wood ER, Eichenbaum H (2000) Neurotoxic hippocampal lesions have no effect on odor span and little effect on odor recognition memory but produce significant impairments on spatial span, recognition, and alternation. J Neurosci 20:2964–2977

    PubMed  CAS  Google Scholar 

  • Dunnett SB (1985) Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats. Psychopharmacology (Berl) 87:357–363

    Article  CAS  Google Scholar 

  • Eagle DM, Baunez C (2010) Is there an inhibitory-response-control system in the rat? Evidence from anatomical and pharmacological studies of behavioral inhibition. Neurosci Biobehav Rev 34:50–72

    Article  PubMed  Google Scholar 

  • Eagle DM, Baunez C, Hutcheson DM, Lehmann O, Shah AP, Robbins TW (2008) Stop-signal reaction-time task performance: role of prefrontal cortex and subthalamic nucleus. Cereb Cortex 18:178–188

    Article  PubMed  Google Scholar 

  • Eagle DM, Robbins TW (2003) Lesions of the medial prefrontal cortex or nucleus accumbens core do not impair inhibitory control in rats performing a stop-signal reaction time task. Behav Brain Res 146:131–144

    Article  PubMed  CAS  Google Scholar 

  • Eagle DM, Tufft MR, Goodchild HL, Robbins TW (2007) Differential effects of modafinil and methylphenidate on stop-signal reaction time task performance in the rat, and interactions with the dopamine receptor antagonist cis-flupenthixol. Psychopharmacology (Berl) 192:193–206

    Article  CAS  Google Scholar 

  • Echevarria DJ, Brewer A, Burk JA, Brown SN, Manuzon H, Robinson JK (2005) Construct validity of an operant signal detection task for rats. Behav Brain Res 157:283–290

    Article  PubMed  Google Scholar 

  • Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 98:6917–6922

    Article  PubMed  CAS  Google Scholar 

  • Erlenmeyer-Kimling L (2000) Neurobehavioral deficits in offspring of schizophrenic parents: liability indicators and predictors of illness. Am J Med Genet 97:65–71

    Article  PubMed  CAS  Google Scholar 

  • Fagerlund B, Mackeprang T, Gade A, Glenthoj BY (2004) Effects of low-dose risperidone and low-dose zuclopenthixol on cognitive functions in first-episode drug-naive schizophrenic patients. CNS Spectr 9:364–374

    PubMed  Google Scholar 

  • Fields RB, Van Kammen DP, Peters JL, Rosen J, Van Kammen WB, Nugent A, Stipetic M, Linnoila M (1988) Clonidine improves memory function in schizophrenia independently from change in psychosis. Preliminary findings. Schizophr Res 1:417–423

    Article  PubMed  CAS  Google Scholar 

  • Fletcher PJ, Tampakeras M, Sinyard J, Higgins GA (2007) Opposing effects of 5-HT(2A) and 5-HT(2 C) receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test. Psychopharmacology (Berl) 195:223–234

    Article  CAS  Google Scholar 

  • Fletcher PJ, Tenn CC, Rizos Z, Lovic V, Kapur S (2005) Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Psychopharmacology (Berl) 183:190–200

    Article  CAS  Google Scholar 

  • Floresco SB, Geyer MA, Gold LH, Grace AA (2005) Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia. Schizophr Bull 31:888–894

    Article  PubMed  Google Scholar 

  • Folley BS, Astur R, Jagannathan K, Calhoun VD, Pearlson GD (2010) Anomalous neural circuit function in schizophrenia during a virtual Morris water task. Neuroimage 49:3373–3384

    Article  PubMed  Google Scholar 

  • Friedman HR, Goldman-Rakic PS (1988) Activation of the hippocampus and dentate gyrus by working-memory: a 2-deoxyglucose study of behaving rhesus monkeys. J Neurosci 8:4693–4706

    PubMed  CAS  Google Scholar 

  • Friedman JI, Adler DN, Temporini HD, Kemether E, Harvey PD, White L, Parrella M, Davis KL (2001) Guanfacine treatment of cognitive impairment in schizophrenia. Neuropsychopharmacology 25:402–409

    Article  PubMed  CAS  Google Scholar 

  • Geyer MA (2010) New opportunities in the treatment of cognitive impairments associated with schizophrenia. Curr Direct Psychol Sci 19:264–269

    Article  Google Scholar 

  • Gibbs SE, D’Esposito M (2005) A functional MRI study of the effects of bromocriptine, a dopamine receptor agonist, on component processes of working memory. Psychopharmacology (Berl) 180:644–653

    Article  CAS  Google Scholar 

  • Goetghebeur P, Dias R (2009) Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat-a back translational study. Psychopharmacology (Berl) 202:287–293

    Article  CAS  Google Scholar 

  • Gold JM, Hahn B, Zhang WW, Robinson BM, Kappenman ES, Beck VM, Luck SJ (2010) Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia. Arch Gen Psychiatry 67:570–577

    Article  PubMed  Google Scholar 

  • Goldberg TE, Weinberger DR (1995) Thought disorder, working memory and attention: interrelationships and the effects of neuroleptic medications. Int Clin Psychopharmacol 10(Suppl 3):99–104

    PubMed  Google Scholar 

  • Goldberg TE, Weinberger DR, Berman KF, Pliskin NH, Podd MH (1987) Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry 44:1008–1014

    Article  PubMed  CAS  Google Scholar 

  • Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330

    PubMed  CAS  Google Scholar 

  • Green MF (2006) Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 67:e12

    Article  PubMed  Google Scholar 

  • Green MF, Marder SR, Glynn SM, McGurk SR, Wirshing WC, Wirshing DA, Liberman RP, Mintz J (2002) The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone. Biol Psychiatry 51:972–978

    Article  PubMed  CAS  Google Scholar 

  • Grottick AJ, Haman M, Wyler R, Higgins GA (2003) Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligands. Neuropsychopharmacology 28:880–887

    PubMed  CAS  Google Scholar 

  • Grottick AJ, Higgins GA (2002) Assessing a vigilance decrement in aged rats: effects of pre-feeding, task manipulation, and psychostimulants. Psychopharmacology (Berl) 164:33–41

    Article  CAS  Google Scholar 

  • Grottick AJ, Trube G, Corrigall WA, Huwyler J, Malherbe P, Wyler R, Higgins GA (2000) Evidence that nicotinic alpha(7) receptors are not involved in the hyperlocomotor and rewarding effects of nicotine. J Pharmacol Exp Ther 294:1112–1119

    PubMed  CAS  Google Scholar 

  • Grottick AJ, Wyler R, Higgins GA (2001) A study of the nicotinic agonist SIB-1553A on locomotion and attention as measured by the five-choice serial reaction time task. Pharmacol Biochem Behav 70:505–513

    Article  PubMed  CAS  Google Scholar 

  • Hagan JJ, Jones DN (2005) Predicting drug efficacy for cognitive deficits in schizophrenia. Schizophr Bull 31:830–853

    Article  PubMed  Google Scholar 

  • Harvey PD, Green MF, McGurk SR, Meltzer HY (2003) Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study. Psychopharmacology (Berl) 169:404–411

    Article  CAS  Google Scholar 

  • Harvey PD, Keefe RS (2001) Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 158:176–184

    Article  PubMed  CAS  Google Scholar 

  • Harvey PD, Meltzer H, Simpson GM, Potkin SG, Loebel A, Siu C, Romano SJ (2004) Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia. Schizophr Res 66:101–113

    Article  PubMed  Google Scholar 

  • Hashimoto K, Fujita Y, Iyo M (2007) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of fluvoxamine: role of sigma-1 receptors. Neuropsychopharmacology 32:514–521

    Article  PubMed  CAS  Google Scholar 

  • Hatcher PD, Brown VJ, Tait DS, Bate S, Overend P, Hagan JJ, Jones DN (2005) 5-HT6 receptor antagonists improve performance in an attentional set shifting task in rats. Psychopharmacology (Berl) 181:253–259

    Article  CAS  Google Scholar 

  • Heinrichs RW (2007) Cognitive improvement in response to antipsychotic drugs: neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 64:631–632

    Article  PubMed  Google Scholar 

  • Hodges H, Green S (1986) Effects of chlordiazepoxide on cued radial maze performance in rats. Psychopharmacology (Berl) 88:460–466

    Article  CAS  Google Scholar 

  • Howe WM, Ji J, Parikh V, Williams S, Mocaer E, Trocme-Thibierge C, Sarter M (2010) Enhancement of attentional performance by selective stimulation of alpha4beta2(*) nAChRs: underlying cholinergic mechanisms. Neuropsychopharmacology 35:1391–1401

    Article  PubMed  CAS  Google Scholar 

  • Hoyle E, Genn RF, Fernandes C, Stolerman IP (2006) Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task. Psychopharmacology (Berl) 189:211–223

    Article  CAS  Google Scholar 

  • Huang YW, Hu WW, Chen Z, Zhang LS, Shen HQ, Timmerman H, Leurs R, Yanai K (2004) Effect of the histamine H3-antagonist clobenpropit on spatial memory deficits induced by MK-801 as evaluated by radial maze in Sprague-Dawley rats. Behav Brain Res 151:287–293

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  • Idris N, Neill J, Grayson B, Bang-Andersen B, Witten LM, Brennum LT, Arnt J (2010) Sertindole improves sub-chronic PCP-induced reversal learning and episodic memory deficits in rodents: involvement of 5-HT(6) and 5-HT (2A) receptor mechanisms. Psychopharmacology (Berl) 208:23–36

    Article  CAS  Google Scholar 

  • Idris NF, Repeto P, Neill JC, Large CH (2005) Investigation of the effects of lamotrigine and clozapine in improving reversal-learning impairments induced by acute phencyclidine and D-amphetamine in the rat. Psychopharmacology (Berl) 179:336–348

    Article  CAS  Google Scholar 

  • Jarrold C, Towse JN (2006) Individual differences in working memory. Neuroscience 139:39–50

    Article  PubMed  CAS  Google Scholar 

  • Jazbec S, Pantelis C, Robbins T, Weickert T, Weinberger DR, Goldberg TE (2007) Intra-dimensional/extra-dimensional set-shifting performance in schizophrenia: impact of distractors. Schizophr Res 89:339–349

    Article  PubMed  Google Scholar 

  • Jeneson A, Mauldin KN, Squire LR (2010) Intact working memory for relational information after medial temporal lobe damage. J Neurosci 30:13624–13629

    Article  PubMed  CAS  Google Scholar 

  • Jennings JW, Keefer LH (1969) Olfactory learning set in two varieties of domestic rat. Psychol Rep 24:3–15

    Article  PubMed  CAS  Google Scholar 

  • Johannsen P (2004) Long-term cholinesterase inhibitor treatment of Alzheimer’s disease. CNS Drugs 18:757–768

    Article  PubMed  CAS  Google Scholar 

  • Jones DN, Higgins GA (1995) Effect of scopolamine on visual attention in rats. Psychopharmacology (Berl) 120:142–149

    Article  CAS  Google Scholar 

  • Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, Lewis SW (2006) Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 63:1079–1087

    Article  PubMed  CAS  Google Scholar 

  • Kane MJ, Engle RW (2002) The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: an individual-differences perspective. Psychon Bull Rev 9:637–671

    Article  PubMed  Google Scholar 

  • Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA (2007) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 64:633–647

    Article  PubMed  CAS  Google Scholar 

  • Keefe RS, Seidman LJ, Christensen BK, Hamer RM, Sharma T, Sitskoorn MM, Rock SL, Woolson S, Tohen M, Tollefson GD, Sanger TM, Lieberman JA (2006) Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Biol Psychiatry 59:97–105

    Article  PubMed  CAS  Google Scholar 

  • Keefe RS, Silva SG, Perkins DO, Lieberman JA (1999) The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 25:201–222

    Article  PubMed  CAS  Google Scholar 

  • Kern RS, Green MF, Marshall BD Jr, Wirshing WC, Wirshing D, McGurk S, Marder SR, Mintz J (1998) Risperidone vs. haloperidol on reaction time, manual dexterity, and motor learning in treatment-resistant schizophrenia patients. Biol Psychiatry 44:726–732

    Article  PubMed  CAS  Google Scholar 

  • Kern RS, Green MF, Marshall BD Jr, Wirshing WC, Wirshing D, McGurk SR, Marder SR, Mintz J (1999) Risperidone versus haloperidol on secondary memory: can newer medications aid learning? Schizophr Bull 25:223–232

    Article  PubMed  CAS  Google Scholar 

  • King MV, Sleight AJ, Woolley ML, Topham IA, Marsden CA, Fone KC (2004) 5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation—an effect sensitive to NMDA receptor antagonism. Neuropharmacology 47:195–204

    Article  PubMed  CAS  Google Scholar 

  • Kirkby DL, Jones DN, Barnes JC, Higgins GA (1996) Effects of anticholinesterase drugs tacrine and E2020, the 5-HT(3) antagonist ondansetron, and the H(3) antagonist thioperamide, in models of cognition and cholinergic function. Behav Pharmacol 7:513–525

    PubMed  CAS  Google Scholar 

  • Kobayashi S, Kametani H, Ugawa Y, Osanai M (1988) Age difference of response strategy in radial maze performance of Fischer-344 rats. Physiol Behav 42:277–280

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Kohler CG, Martin EA, Kujawski E, Bilker W, Gur RE, Gur RC (2007) No effect of donepezil on neurocognition and social cognition in young persons with stable schizophrenia. Cognit Neuropsychiatry 12:412–421

    Article  Google Scholar 

  • Kraepelin E (1893) Ein kurzes Lahrbruch fur Studirende und Aerzte Leipzig Verlag von Ambr. Abel 4e Auflage, Heidelberg, pp 435–445

    Google Scholar 

  • Kunitachi S, Fujita Y, Ishima T, Kohno M, Horio M, Tanibuchi Y, Shirayama Y, Iyo M, Hashimoto K (2009) Phencyclidine-induced cognitive deficits in mice are ameliorated by subsequent subchronic administration of donepezil: role of sigma-1 receptors. Brain Res 1279:189–196

    Article  PubMed  CAS  Google Scholar 

  • Lapiz MD, Morilak DA (2006) Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capability. Neuroscience 137:1039–1049

    Article  PubMed  CAS  Google Scholar 

  • Laurent A, Saoud M, Bougerol T, d’Amato T, Anchisi AM, Biloa-Tang M, Dalery J, Rochet T (1999) Attentional deficits in patients with schizophrenia and in their non-psychotic first-degree relatives. Psychiatry Res 89:147–59

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Park S (2005) Working memory impairments in schizophrenia: a meta-analysis. J Abnorm Psychol 114:599–611

    Article  PubMed  Google Scholar 

  • Leeson VC, Robbins TW, Matheson E, Hutton SB, Ron MA, Barnes TR, Joyce EM (2009) Discrimination learning, reversal, and set-shifting in first-episode schizophrenia: stability over six years and specific associations with medication type and disorganization syndrome. Biol Psychiatry 66:586–593

    Article  PubMed  Google Scholar 

  • Leonard J (1959) Five-choice serial reaction apparatus. Medical Research Council Applied Psychology Reports, Cambridge

    Google Scholar 

  • Levin ED (2002) Nicotinic receptor subtypes and cognitive function. J Neurobiol 53:633–640

    Article  PubMed  CAS  Google Scholar 

  • Levin ED, Bradley A, Addy N, Sigurani N (2002) Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors and working memory. Neuroscience 109:757–765

    Article  PubMed  CAS  Google Scholar 

  • Levin ED, Kim P, Meray R (1996) Chronic nicotine working and reference memory effects in the 16-arm radial maze: interactions with D1 agonist and antagonist drugs. Psychopharmacology (Berl) 127:25–30

    Article  CAS  Google Scholar 

  • Levin ED, Simon BB (1998) Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology (Berl) 138:217–230

    Article  CAS  Google Scholar 

  • Lewis SW, Barnes TR, Davies L, Murray RM, Dunn G, Hayhurst KP, Markwick A, Lloyd H, Jones PB (2006) Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophr Bull 32:715–723

    Article  PubMed  Google Scholar 

  • Lindner MD, Hogan JB, Hodges DB Jr, Orie AF, Chen P, Corsa JA, Leet JE, Gillman KW, Rose GM, Jones KM, Gribkoff VK (2006) Donepezil primarily attenuates scopolamine-induced deficits in psychomotor function, with moderate effects on simple conditioning and attention, and small effects on working memory and spatial mapping. Psychopharmacology (Berl) 188:629–640

    Article  CAS  Google Scholar 

  • Logan GD, Cowan WB, Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform 10:276–291

    Article  PubMed  CAS  Google Scholar 

  • Lyon M (1991) Animal models of mania and schizophrenia. In: Willner P (ed) Behavioural models in psychopharmacology: Theoretical. Cambridge University, Cambridge, Industrial and clinical perspectives, pp 253–310

    Google Scholar 

  • Marder SR, Fenton W (2004) Measurement and Treatment Research to Improve Cognition in Schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res 72:5–9

    Article  PubMed  Google Scholar 

  • Markham MR, Butt AE, Dougher MJ (1996) A computer touch-screen apparatus for training visual discriminations in rats. J Exp Anal Behav 65:173–182

    Article  PubMed  CAS  Google Scholar 

  • Marston HM (1996) Analysis of cognitive function in animals, the value of SDT. Brain Res Cogn Brain Res 3:269–277

    Article  PubMed  CAS  Google Scholar 

  • Martin LF, Kem WR, Freedman R (2004) Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl) 174:54–64

    Article  CAS  Google Scholar 

  • Martinez V, Sarter M (2008) Detection of the moderately beneficial cognitive effects of low-dose treatment with haloperidol or clozapine in an animal model of the attentional impairments of schizophrenia. Neuropsychopharmacology 33:2635–2647

    Article  PubMed  CAS  Google Scholar 

  • Matthysse S (1986) Animal models in psychiatric research. Prog Brain Res 65:259–270

    Article  PubMed  CAS  Google Scholar 

  • Mathes B, Wood SJ, Proffitt TM, Stuart GW, Buchanan JA, Velakoulis D, Brewer WJ, McGorry PD, Pantelis C (2005) Early processing deficits in object working memory in first-episode schizophreniform psychosis and established schizophrenia. Psychol Med 35:1053–1062

    Article  PubMed  Google Scholar 

  • McGaughy J, Kaiser T, Sarter M (1996) Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density. Behav Neurosci 110:247–265

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • McLean SL, Beck JP, Woolley ML, Neill JC (2008) A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats. Behav Brain Res 189:152–158

    Article  PubMed  CAS  Google Scholar 

  • McLean SL, Grayson B, Harris M, Protheroe C, Bate S, Woolley ML, Neill JC (2010) Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats. J Psychopharmacol 24:57–63

    Article  PubMed  Google Scholar 

  • Mehta MA, Swainson R, Ogilvie AD, Sahakian J, Robbins TW (2001) Improved short-term spatial memory but impaired reversal learning following the dopamine D(2) agonist bromocriptine in human volunteers. Psychopharmacology (Berl) 159:10–20

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Micheau J, Riedel G, Roloff EL, Inglis J, Morris RG (2004) Reversible hippocampal inactivation partially dissociates how and where to search in the water maze. Behav Neurosci 118:1022–1032

    Article  PubMed  CAS  Google Scholar 

  • Min SK, Moon IW, Ko RW, Shin HS (2001) Effects of transdermal nicotine on attention and memory in healthy elderly non-smokers. Psychopharmacology (Berl) 159:83–88

    Article  CAS  Google Scholar 

  • Mori K, Obara Y, Moriya T, Inatomi S, Nakahata N (2011) Effects of Hericium erinaceus on amyloid beta(25-35) peptide-induced learning and memory deficits in mice. Biomed Res 32:67–72

    Article  PubMed  CAS  Google Scholar 

  • Morris RGM (1981) Spatial localization does not require the presence of local cues. Learning Motivation 12:239

    Article  Google Scholar 

  • Muir JL, Dunnett SB, Robbins TW, Everitt BJ (1992) Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task. Exp Brain Res 89:611–622

    Article  PubMed  CAS  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 (Berl) 118:82–92

    Article  CAS  Google Scholar 

  • Muir JL, Everitt BJ, Robbins TW (1996) The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task. Cereb Cortex 6:470–481

    Article  PubMed  CAS  Google Scholar 

  • Muir JL, Fischer W, Bjorklund A (1999) Decline in visual attention and spatial memory in aged rats. Neurobiol Aging 20:605–615

    Article  PubMed  CAS  Google Scholar 

  • Muller U, von Cramon DY, Pollmann S (1998) D1- versus D2-receptor modulation of visuospatial working memory in humans. J Neurosci 18:2720–2728

    PubMed  CAS  Google Scholar 

  • Murray GK, Cheng F, Clark L, Barnett JH, Blackwell AD, Fletcher PC, Robbins TW, Bullmore ET, Jones PB (2008) Reinforcement and reversal learning in first-episode psychosis. Schizophr Bull 34:848–855

    Article  PubMed  CAS  Google Scholar 

  • Mutlu O, Ulak G, Celikyurt IK, Akar FY, Erden F (2011) Effects of olanzapine, sertindole and clozapine on learning and memory in the Morris water maze test in naive and MK-801-treated mice. Pharmacol Biochem Behav 98:398–404

    Article  PubMed  CAS  Google Scholar 

  • Nagai T, Murai R, Matsui K, Kamei H, Noda Y, Furukawa H, Nabeshima T (2009) Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors. Psychopharmacology (Berl) 202:315–328

    Article  CAS  Google Scholar 

  • Navarra R, Graf R, Huang Y, Logue S, Comery T, Hughes Z, Day M (2008) Effects of atomoxetine and methylphenidate on attention and impulsivity in the 5-choice serial reaction time test. Prog Neuropsychopharmacol Biol Psychiatry 32:34–41

    Article  PubMed  CAS  Google Scholar 

  • Newhouse P, Singh A, Potter A (2004) Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem 4:267–282

    Article  PubMed  CAS  Google Scholar 

  • Nieuwenstein MR, Aleman A, de Haan EH (2001) 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  PubMed  CAS  Google Scholar 

  • Niimi K, Takahashi E, Itakura C (2008) Improved short-term memory and increased expression of NR2B observed in senescence-accelerated mouse (SAM) P6. Exp Gerontol 43:847–852

    Article  PubMed  CAS  Google Scholar 

  • Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK (2004) Identification of separable cognitive factors in schizophrenia. Schizophr Res 72:29–39

    Article  PubMed  Google Scholar 

  • Nuechterlein KH, Luck SJ, Lustig C, Sarter M (2009) CNTRICS final task selection: control of attention. Schizophr Bull 35:182–196

    Article  PubMed  Google Scholar 

  • Olton DS, Samuelson RJ (1976) Remembrance of places passed: Spatial memory in rats. J Exp Psychol Anim Behav Proc 2:97–116

    Article  Google Scholar 

  • Olton DS, Werz MA (1978) Hippocampal function and behavior: spatial discrimination and response inhibition. Physiol Behav 20:597–605

    Article  PubMed  CAS  Google Scholar 

  • Owen AM, Roberts AC, Polkey CE, Sahakian BJ, Robbins TW (1991) Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 29:993–1006

    Article  PubMed  CAS  Google Scholar 

  • Paine TA, Neve RL, Carlezon WA Jr (2009) Attention deficits and hyperactivity following inhibition of cAMP-dependent protein kinase within the medial prefrontal cortex of rats. Neuropsychopharmacology 34:2143–2155

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Pantelis C, Barnes TR, Nelson HE, Tanner S, Weatherley L, Owen AM, Robbins TW (1997) Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain 120(Pt 10):1823–1843

    Article  PubMed  Google Scholar 

  • Parasuraman R (1998) The attentive brain. MIT Press, MA, USA

    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(12):1254–1268

    Google Scholar 

  • Pattij T, Janssen MC, Loos M, Smit AB, Schoffelmeer AN, van Gaalen MM (2007) Strain specificity and cholinergic modulation of visuospatial attention in three inbred mouse strains. Genes Brain Behav 6:579–587

    Article  PubMed  CAS  Google Scholar 

  • Pietrzak RH, Snyder PJ, Maruff P (2010) Amphetamine-related improvement in executive function in patients with chronic schizophrenia is modulated by practice effects. Schizophr Res 124:176–182

    Article  PubMed  Google Scholar 

  • Prouteau A, Verdoux H, Briand C, Lesage A, Lalonde P, Nicole L, Reinharz D, Stip E (2004) The crucial role of sustained attention in community functioning in outpatients with schizophrenia. Psychiatry Res 129:171–177

    Article  PubMed  Google Scholar 

  • Purdon SE, Malla A, Labelle A, Lit W (2001) Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. J Psychiatry Neurosci 26:137–149

    PubMed  CAS  Google Scholar 

  • Ragland JD, Cools R, Frank M, Pizzagalli DA, Preston A, Ranganath C, Wagner AD (2009) CNTRICS final task selection: long-term memory. Schizophr Bull 35:197–212

    Article  PubMed  Google Scholar 

  • Rausch R, Babb TL (1993) Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. Arch Neurol 50:812–817

    Article  PubMed  CAS  Google Scholar 

  • Reeves SJ, Grasby PM, Howard RJ, Bantick RA, Asselin MC, Mehta MA (2005) A positron emission tomography (PET) investigation of the role of striatal dopamine (D2) receptor availability in spatial cognition. Neuroimage 28:216–226

    Article  PubMed  Google Scholar 

  • Rezvani AH, Caldwell DP, Levin ED (2005) Nicotinic-serotonergic drug interactions and attentional performance in rats. Psychopharmacology (Berl) 179:521–528

    Article  CAS  Google Scholar 

  • Rezvani AH, Levin ED (2001) Cognitive effects of nicotine. Biol Psychiatry 49:258–267

    Article  PubMed  CAS  Google Scholar 

  • Rezvani AH, Levin ED (2003) Nicotinic-glutamatergic interactions and attentional performance on an operant visual signal detection task in female rats. Eur J Pharmacol 465:83–90

    Article  PubMed  CAS  Google Scholar 

  • Riccio CA, Reynolds CR, Lowe P, Moore JJ (2002) The continuous performance test: a window on the neural substrates for attention? Arch Clin Neuropsychol 17:235–272

    PubMed  Google Scholar 

  • Richelson E, Souder T (2000) Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci 68:29–39

    Article  PubMed  CAS  Google Scholar 

  • Rinberg D, Koulakov A, Gelperin A (2006) Speed-accuracy tradeoff in olfaction. Neuron 51:351–358

    Article  PubMed  CAS  Google Scholar 

  • Ritsner MS, Blumenkrantz H (2007) Predicting domain-specific insight of schizophrenia patients from symptomatology, multiple neurocognitive functions, and personality related traits. Psychiatry Res 149:59–69

    Article  PubMed  Google Scholar 

  • Robbins TW (1998) Arousal and attention: psychopharmacological and neuropsychophysical studies in experimental animals. In: Parasuraman R (ed) The attentive brain. MIT Press, Cambridge

    Google Scholar 

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

    Article  CAS  Google Scholar 

  • Robinson ES, Eagle DM, Mar AC, Bari A, Banerjee G, Jiang X, Dalley JW, Robbins TW (2008) Similar effects of the selective noradrenaline reuptake inhibitor atomoxetine on three distinct forms of impulsivity in the rat. Neuropsychopharmacology 33:1028–1037

    Article  PubMed  CAS  Google Scholar 

  • Rollnik JD, Borsutzky M, Huber TJ, Mogk H, Seifert J, Emrich HM, Schneider U (2002) Short-term cognitive improvement in schizophrenics treated with typical and atypical neuroleptics. Neuropsychobiology 45:74–80

    Article  PubMed  CAS  Google Scholar 

  • Rosvold H, Sarason AM, Bransome ADJ, Beck LH (1956) A continuous performance test of brain damage. J Consult Psychol 20:343–350

    Article  PubMed  Google Scholar 

  • Roth BL, Hanizavareh SM, Blum AE (2004) Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psychopharmacology (Berl) 174:17–24

    Article  CAS  Google Scholar 

  • Rushforth SL, Allison C, Wonnacott S, Shoaib M (2010) Subtype-selective nicotinic agonists enhance olfactory working memory in normal rats: a novel use of the odour span task. Neurosci Lett 471:114–118

    Article  PubMed  CAS  Google Scholar 

  • Rusted JM, Warburton DM (1992) Facilitation of memory by post-trial administration of nicotine: evidence for an attentional explanation. Psychopharmacology (Berl) 108:452–455

    Article  CAS  Google Scholar 

  • Salgado-Pineda P, Baeza I, Perez-Gomez M, Vendrell P, Junque C, Bargallo N, Bernardo M (2003) Sustained attention impairment correlates to gray matter decreases in first episode neuroleptic-naive schizophrenic patients. Neuroimage 19:365–375

    Article  PubMed  Google Scholar 

  • Sarter M, Martinez V, Kozak R (2009) A neurocognitive animal model dissociating between acute illness and remission periods of schizophrenia. Psychopharmacology (Berl) 202:237–258

    Article  CAS  Google Scholar 

  • Sarter M, McGaughy J (1998) Assessment of sustained and divided attention in rats: aspects of validity; comment. Psychopharmacology (Berl) 138:260–2, discussion 263-5

    Article  CAS  Google Scholar 

  • Sass KJ, Spencer DD, Kim JH, Westerveld M, Novelly RA, Lencz T (1990) Verbal memory impairment correlates with hippocampal pyramidal cell density. Neurology 40:1694–1697

    Article  PubMed  CAS  Google Scholar 

  • Sharma T, Mockler D (1998) The cognitive efficacy of atypical antipsychotics in schizophrenia. J Clin Psychopharmacol 18:12S–19S

    Article  PubMed  CAS  Google Scholar 

  • Sharma T, Reed C, Aasen I, Kumari V (2006) Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation. Schizophr Res 85:73–83

    Article  PubMed  Google Scholar 

  • Silvers JM, Harrod SB, Mactutus CF, Booze RM (2007) Automation of the novel object recognition task for use in adolescent rats. J Neurosci Methods 166:99–103

    Article  PubMed  Google Scholar 

  • Slotnick B (2001) Animal cognition and the rat olfactory system. Trends Cogn Sci 5:216–222

    Article  PubMed  Google Scholar 

  • Slotnick BM, Risser JM (1990) Odor memory and odor learning in rats with lesions of the lateral olfactory tract and mediodorsal thalamic nucleus. Brain Res 529:23–29

    Article  PubMed  CAS  Google Scholar 

  • Smith RC, Warner-Cohen J, Matute M, Butler E, Kelly E, Vaidhyanathaswamy S, Khan A (2006) Effects of nicotine nasal spray on cognitive function in schizophrenia. Neuropsychopharmacology 31:637–643

    Article  PubMed  CAS  Google Scholar 

  • Steckler T, Muir JL (1996) Measurement of cognitive function: relating rodent performance with human minds. Brain Res Cogn Brain Res 3:299–308

    Article  PubMed  CAS  Google Scholar 

  • Stip E, Sepehry AA, Chouinard S (2007) Add-on therapy with acetylcholinesterase inhibitors for memory dysfunction in schizophrenia: a systematic quantitative review, part 2. Clin Neuropharmacol 30:218–229

    PubMed  CAS  Google Scholar 

  • Swerdlow NR (2011) Are we studying and treating schizophrenia correctly? Schizophr Res 130:1–10

    Article  PubMed  Google Scholar 

  • Tarantino IS, Sharp RF, Geyer MA, Meves JM, Young JW (2011) Working memory span capacity improved by a D2 but not D1 receptor family agonist. Behav Brain Res 219:181–188

    Article  PubMed  CAS  Google Scholar 

  • Thomsen MS, Christensen DZ, Hansen HH, Redrobe JP, Mikkelsen JD (2009) Alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment. Neuropharmacology 56:1001–1009

    Article  PubMed  CAS  Google Scholar 

  • Titone D, Ditman T, Holzman PS, Eichenbaum H, Levy DL (2004) Transitive inference in schizophrenia: impairments in relational memory organization. Schizophr Res 68:235–247

    Article  PubMed  Google Scholar 

  • Tunbridge EM, Bannerman DM, Sharp T, Harrison PJ (2004) Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J Neurosci 24:5331–5335

    Article  PubMed  CAS  Google Scholar 

  • Turchi J, Holley LA, Sarter M (1995) Effects of nicotinic acetylcholine receptor ligands on behavioral vigilance in rats. Psychopharmacology (Berl) 118:195–205

    Article  CAS  Google Scholar 

  • Turchi J, Sarter M (2000) Cortical cholinergic inputs mediate processing capacity: effects of 192 IgG-saporin-induced lesions on olfactory span performance. Eur J Neurosci 12:4505–4514

    PubMed  CAS  Google Scholar 

  • Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ (2004a) Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 55:1031–1040

    Article  PubMed  CAS  Google Scholar 

  • Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ (2004b) Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology 29:1363–1373

    Article  PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Twamley EW, Burton CZ, Vella L (2011) Compensatory cognitive training for psychosis: who benefits? Who stays in treatment? Schizophr Bull 37(Suppl 2):S55–S62

    Article  PubMed  Google Scholar 

  • Uchida N, Mainen ZF (2003) Speed and accuracy of olfactory discrimination in the rat. Nat Neurosci 6:1224–1229

    Article  PubMed  CAS  Google Scholar 

  • Velligan DI, Newcomer J, Pultz J, Csernansky J, Hoff AL, Mahurin R, Miller AL (2002) Does cognitive function improve with quetiapine in comparison to haloperidol? Schizophr Res 53:239–248

    Article  PubMed  Google Scholar 

  • Velligan DI, Prihoda TJ, Sui D, Ritch JL, Maples N, Miller AL (2003) The effectiveness of quetiapine versus conventional antipsychotics in improving cognitive and functional outcomes in standard treatment settings. J Clin Psychiatry 64:524–531

    Article  PubMed  CAS  Google Scholar 

  • Wang D, Noda Y, Zhou Y, Nitta A, Furukawa H, Nabeshima T (2007) Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model. Neuropharmacology 52:1179–1187

    Article  PubMed  CAS  Google Scholar 

  • Warburton DM, Rusted JM, Fowler J (1992) A comparison of the attentional and consolidation hypotheses for the facilitation of memory by nicotine. Psychopharmacology (Berl) 108:443–447

    Article  CAS  Google Scholar 

  • Wenk GL (2004) Assessment of spatial memory using the radial arm maze and Morris water maze. Curr Protoc Neurosci Chapter 8: Unit 8 5A

    Google Scholar 

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

    Article  CAS  Google Scholar 

  • Widholm JJ, Clarkson GB, Strupp BJ, Crofton KM, Seegal RF, Schantz SL (2001) Spatial reversal learning in Aroclor 1254-exposed rats: sex-specific deficits in associative ability and inhibitory control. Toxicol Appl Pharmacol 174:188–198

    Article  PubMed  CAS  Google Scholar 

  • Widholm JJ, Seo BW, Strupp BJ, Seegal RF, Schantz SL (2003) Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats. Neurotoxicol Teratol 25:459–471

    Article  PubMed  CAS  Google Scholar 

  • Wietrzych M, Meziane H, Sutter A, Ghyselinck N, Chapman PF, Chambon P, Krezel W (2005) Working memory deficits in retinoid X receptor gamma-deficient mice. Learn Mem 12:318–326

    Article  PubMed  Google Scholar 

  • Yamada M, Hayashida M, Zhao Q, Shibahara N, Tanaka K, Miyata T, Matsumoto K (2011) Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice. J Ethnopharmacol 135(3):737–46

    Article  PubMed  Google Scholar 

  • Young JW, Crawford N, Kelly JS, Kerr LE, Marston HM, Spratt C, Finlayson K, Sharkey J (2007a) Impaired attention is central to the cognitive deficits observed in alpha 7 deficient mice. Eur Neuropsychopharmacol 17:145–155

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Finlayson K, Spratt C, Marston HM, Crawford N, Kelly JS, Sharkey J (2004) Nicotine improves sustained attention in mice: evidence for involvement of the alpha7 nicotinic acetylcholine receptor. Neuropsychopharmacology 29:891–900

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Geyer MA (2010) Action of modafinil-increased motivation via the dopamine transporter inhibition and D1 receptors? Biol Psychiatry 67:784–787

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Geyer MA, subcommittee p (2007b) Report on putative preclinical models of the MATRICS battery. http://www.turns.ucla.edu/preclinical-TURNS-report-2006b.pdf

  • Young JW, Henry BL, Geyer MA (2011a) Predictive animal models of mania: hits, misses and future directions. Br J Pharmacol 164:1263–1284

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Kerr LE, Kelly JS, Marston HM, Spratt C, Finlayson K, Sharkey J (2007c) The odour span task: a novel paradigm for assessing working memory in mice. Neuropharmacology 52:634–645

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Light GA, Marston HM, Sharp R, Geyer MA (2009a) The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS One 4:e4227

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Meves JM, Tarantino IS, Caldwell S, Geyer MA (2011b) Delayed procedural learning in alpha7-nicotinic acetylcholine receptor knockout mice. Genes Brain Behav 10:720–733

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Powell SB, Geyer MA (2011c) Mouse pharmacological models of cognitive disruption relevant to schizophrenia. Neuropharmacology 62(3):1381–90

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Powell SB, Risbrough V, Marston HM, Geyer MA (2009b) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 122:150–202

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Powell SB, Scott CN, Zhou X, Geyer MA (2011d) The effect of reduced dopamine D4 receptor expression in the 5-choice continuous performance task: Separating response inhibition from premature responding. Behav Brain Res 222:183–192

    Article  PubMed  CAS  Google Scholar 

  • Young JW, Sharkey J, Finlayson K (2009c) Progressive impairment in olfactory working memory in a mouse model of mild cognitive impairment. Neurobiol Aging 30:1430–1443

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Institute of Mental Health (MH042228, MH071916, MH091571) and the U.S. Veterans Administration, Veterans Integrated Service Network (VISN) 22 Mental Illness Research, Education, and Clinical Center.

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Correspondence to Jared W. Young .

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Young, J.W., Amitai, N., Geyer, M.A. (2012). Behavioral Animal Models to Assess Pro-cognitive Treatments for Schizophrenia. In: Geyer, M., Gross, G. (eds) Novel Antischizophrenia Treatments. Handbook of Experimental Pharmacology, vol 213. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25758-2_3

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