Psychopharmacology

, Volume 219, Issue 2, pp 253–270

Measuring impulsivity in mice: the five-choice serial reaction time task

  • Sandra Sanchez-Roige
  • Yolanda Peña-Oliver
  • David N. Stephens
Review

Abstract

Rationale

Mice are useful tools for dissecting genetic and environmental factors in relation to the study of attention and impulsivity. The five-choice serial reaction time task (5CSRTT) paradigm has been well established in rats, but its transferability to mice is less well documented.

Objectives

This study aims to summarise the main results of the 5CSRTT in mice, with special focus on impulsivity.

Methods

The 5CSRTT can be used to explore aspects of both attentional and inhibitory control mechanisms.

Results

Different manipulations of the task parameters can lead to different results; adjusting the protocol as a function of the main variable of interest or the standardisation of the protocol to be applied to a large set of strains will be desirable.

Conclusions

The 5CSRTT has proven to be a useful tool to investigate impulsivity in mice.

Keywords

Five-choice serial reaction time task Impulsivity Attention Task parameters Mice 

References

  1. Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25:239–252PubMedCrossRefGoogle Scholar
  2. Amitai N, Markou A (2010) Disruption of performance in the five-choice serial reaction time task induced by administration of N-methyl-D-aspartate receptor antagonists: relevance to cognitive dysfunction in schizophrenia. Biol Psychiatry 68:5–16PubMedCrossRefGoogle Scholar
  3. Anwar S, Peters O, Millership S, Ninkina N, Doig N, Connor-Robson N, Threlfell S, Kooner G, Deacon RM, Bannerman DM, Bolam JP, Chandra SS, Cragg SJ, Wade-Martins R, Buchman VL (2011) Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family. J Neurosci 31:7264–7274PubMedCrossRefGoogle Scholar
  4. Ataman B, Ashley J, Gorczyca M, Ramachandran P, Fouquet W, Sigrist SJ, Budnik V (2008) Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling. Neuron 57:705–718PubMedCrossRefGoogle Scholar
  5. Bailey CD, De Biasi M, Fletcher PJ, Lambe EK (2010) The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy. J Neurosci 30:9241–9252PubMedGoogle Scholar
  6. Bari A, Dalley JW, Robbins TW (2008) The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats. Nat Protoc 3:759–767PubMedCrossRefGoogle Scholar
  7. Bizarro L, Patel S, Stolerman IP (2003) Comprehensive deficits in performance of an attentional task produced by co-administering alcohol and nicotine to rats. Drug Alcohol Depend 72:287–295PubMedCrossRefGoogle Scholar
  8. Bovolenta P, Rodriguez J, Esteve P (2006) Frizzled/RYK mediated signalling in axon guidance. Development 133:4399–4408PubMedCrossRefGoogle Scholar
  9. 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 9:361–380PubMedCrossRefGoogle Scholar
  10. Chesler EJ, Wang J, Lu L, Qu Y, Manly KF, Williams RW (2003) Genetic correlates of gene expression in recombinant inbred strains: a relational model system to explore neurobehavioral phenotypes. Neuroinformatics 1:343–357PubMedCrossRefGoogle Scholar
  11. Christakou A, Robbins TW, Everitt BJ (2004) Prefrontal cortical-ventral striatal interactions involved in affective modulation of attentional performance: implications for corticostriatal circuit function. J Neurosci 24:773–780PubMedCrossRefGoogle Scholar
  12. Clark L, Robbins T (2002) Decision-making deficits in drug addiction. Trends Cogn Sci 6:361PubMedCrossRefGoogle Scholar
  13. Coull JT, Cheng RK, Meck WH (2011) Neuroanatomical and neurochemical substrates of timing. Neuropsychopharmacology 36:3–25PubMedCrossRefGoogle Scholar
  14. Crabbe JC, Phillips TJ, Buck KJ, Cunningham CL, Belknap JK (1999) Identifying genes for alcohol and drug sensitivity: recent progress and future directions. Trends Neurosci 22:173–179PubMedCrossRefGoogle Scholar
  15. Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R (1997) Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology (Berl) 132:107–124CrossRefGoogle Scholar
  16. Dalley JW, Theobald DE, Eagle DM, Passetti F, Robbins TW (2002) Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex. Neuropsychopharmacology 26:716–728PubMedCrossRefGoogle Scholar
  17. Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784PubMedCrossRefGoogle Scholar
  18. Dalley JW, Laane K, Theobald DE, Pena Y, Bruce CC, Huszar AC, Wojcieszek M, Everitt BJ, Robbins TW (2007) Enduring deficits in sustained visual attention during withdrawal of intravenous methylenedioxymethamphetamine self-administration in rats: results from a comparative study with d-amphetamine and methamphetamine. Neuropsychopharmacology 32:1195–1206PubMedCrossRefGoogle Scholar
  19. Dalley JW, Mar AC, Economidou D, Robbins TW (2008) Neurobehavioral mechanisms of impulsivity: fronto-striatal systems and functional neurochemistry. Pharmacol Biochem Behav 90:250–260PubMedCrossRefGoogle Scholar
  20. Dalley JW, Everitt BJ, Robbins TW (2011) Impulsivity, compulsivity, and top-down cognitive control. Neuron 69:680–694PubMedCrossRefGoogle Scholar
  21. Davies W, Humby T, Isles AR, Burgoyne PS, Wilkinson LS (2007) X-monosomy effects on visuospatial attention in mice: a candidate gene and implications for Turner syndrome and attention deficit hyperactivity disorder. Biol Psychiatry 61:1351–1360PubMedCrossRefGoogle Scholar
  22. Davies W, Humby T, Kong W, Otter T, Burgoyne PS, Wilkinson LS (2009) Converging pharmacological and genetic evidence indicates a role for steroid sulfatase in attention. Biol Psychiatry 66:360–367PubMedCrossRefGoogle Scholar
  23. de Bruin NM, Fransen F, Duytschaever H, Grantham C, Megens AA (2006) Attentional performance of (C57BL/6Jx129Sv)F2 mice in the five-choice serial reaction time task. Physiol Behav 89:692–703PubMedCrossRefGoogle Scholar
  24. Duka T, Trick L, Nikolaou K, Gray MA, Kempton MJ, Williams H, Williams SC, Critchley HD, Stephens DN (2011) Unique brain areas associated with abstinence control are damaged in multiply detoxified alcoholics. Biol Psychiatry. doi:10.1016/j.biopsych.2011.04.006
  25. El-Kordi A, Radyushkin K, Ehrenreich H (2009) Erythropoietin improves operant conditioning and stability of cognitive performance in mice. BMC Biol 7:37PubMedCrossRefGoogle Scholar
  26. Evenden JL (1999) Varieties of impulsivity. Psychopharmacology (Berl) 146:348–361CrossRefGoogle Scholar
  27. Fletcher PJ, Tampakeras M, Sinyard J, Higgins GA (2007) Opposing effects of 5-HT(2A) and 5-HT(2C) receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test. Psychopharmacology (Berl) 195:223–234CrossRefGoogle Scholar
  28. Greco B, Carli M (2006) Reduced attention and increased impulsivity in mice lacking NPY Y2 receptors: relation to anxiolytic-like phenotype. Behav Brain Res 169:325–334PubMedCrossRefGoogle Scholar
  29. Greco B, Invernizzi RW, Carli M (2005) Phencyclidine-induced impairment in attention and response control depends on the background genotype of mice: reversal by the mGLU(2/3) receptor agonist LY379268. Psychopharmacology (Berl) 179:68–76CrossRefGoogle Scholar
  30. Hahn B, Stolerman IP (2002) Nicotine-induced attentional enhancement in rats: effects of chronic exposure to nicotine. Neuropsychopharmacology 27:712–722PubMedCrossRefGoogle Scholar
  31. 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 (Berl) 162:129–137CrossRefGoogle Scholar
  32. 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 (Berl) 133:329–342CrossRefGoogle Scholar
  33. 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) 189:211–223CrossRefGoogle Scholar
  34. Humby T, Laird FM, Davies W, Wilkinson LS (1999) Visuospatial attentional functioning in mice: interactions between cholinergic manipulations and genotype. Eur J Neurosci 11:2813–2823PubMedCrossRefGoogle Scholar
  35. Humby T, Wilkinson L, Dawson G (2005) Assaying aspects of attention and impulse control in mice using the 5-choice serial reaction time task. Curr Protoc Neurosci Chapter 8: Unit 8 5HGoogle Scholar
  36. Isles AR, Humby T, Walters E, Wilkinson LS (2004) Common genetic effects on variation in impulsivity and activity in mice. J Neurosci 24:6733–6740PubMedCrossRefGoogle Scholar
  37. Kerns RT, Ravindranathan A, Hassan S, Cage MP, York T, Sikela JM, Williams RW, Miles MF (2005) Ethanol-responsive brain region expression networks: implications for behavioral responses to acute ethanol in DBA/2J versus C57BL/6J mice. J Neurosci 25:2255–2266PubMedCrossRefGoogle Scholar
  38. Kerr LE, McGregor AL, Amet LE, Asada T, Spratt C, Allsopp TE, Harmar AJ, Shen S, Carlson G, Logan N, Kelly JS, Sharkey J (2004) Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia. Cell Death Differ 11:1102–1111PubMedCrossRefGoogle Scholar
  39. Lambourne SL, Humby T, Isles AR, Emson PC, Spillantini MG, Wilkinson LS (2007) Impairments in impulse control in mice transgenic for the human FTDP-17 tauV337M mutation are exacerbated by age. Hum Mol Genet 16:1708–1719PubMedCrossRefGoogle Scholar
  40. Lawrence AD, Sahakian BJ (1995) Alzheimer disease, attention, and the cholinergic system. Alzheimer Dis Assoc Disord 9(Suppl 2):43–49PubMedGoogle Scholar
  41. Lee B, Tumu P, Paul IA (2002) Effects of LP-BM5 murine leukemia virus infection on errors and response time in a two-choice serial reaction time task in C57BL/6 mice. Brain Res 948:1–7PubMedCrossRefGoogle Scholar
  42. Loos M, van der Sluis S, Bochdanovits Z, van Zutphen IJ, Pattij T, Stiedl O, Smit AB, Spijker S (2009) Activity and impulsive action are controlled by different genetic and environmental factors. Genes Brain Behav 8:817–828PubMedCrossRefGoogle Scholar
  43. Loos M, Staal J, Schoffelmeer AN, Smit AB, Spijker S, Pattij T (2010) Inhibitory control and response latency differences between C57BL/6J and DBA/2J mice in a Go/No-Go and 5-choice serial reaction time task and strain-specific responsivity to amphetamine. Behav Brain Res 214:216–224PubMedCrossRefGoogle Scholar
  44. Marston HM, Spratt C, Kelly JS (2001) Phenotyping complex behaviours: assessment of circadian control and 5-choice serial reaction learning in the mouse. Behav Brain Res 125:189–193PubMedCrossRefGoogle Scholar
  45. Oliver YP, Ripley TL, Stephens DN (2009) Ethanol effects on impulsivity in two mouse strains: similarities to diazepam and ketamine. Psychopharmacology (Berl) 204:679–692CrossRefGoogle Scholar
  46. Otsuki T, Kajigaya S, Ozawa K, Liu JM (1999) SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein. Biochem Biophys Res Commun 265:630–635PubMedCrossRefGoogle Scholar
  47. Patel S, Stolerman IP, Asherson P, Sluyter F (2006) Attentional performance of C57BL/6 and DBA/2 mice in the 5-choice serial reaction time task. Behav Brain Res 170:197–203PubMedCrossRefGoogle Scholar
  48. Pattij T, Vanderschuren LJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29:192–199PubMedCrossRefGoogle Scholar
  49. 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 6:579–587PubMedCrossRefGoogle Scholar
  50. Peña-Oliver Y, Buchman V, Dalley J, Robbins TW, Schumann G, Ripley T, King S, Stephens D (2011) Deletion of alpha-synuclein decreases impulsivity in mice. Genes, Brain and Behaviour (in press)Google Scholar
  51. Phillips TJ, Huson MG, McKinnon CS (1998) Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice. J Neurosci 18:3023–3034PubMedGoogle Scholar
  52. Pozzi L, Greco B, Sacchetti G, Leoni G, Invernizzi RW, Carli M (2010) Blockade of serotonin 2A receptors prevents PCP-induced attentional performance deficit and CREB phosphorylation in the dorsal striatum of DBA/2 mice. Psychopharmacology (Berl) 208:387–399CrossRefGoogle Scholar
  53. Relkovic D, Doe CM, Humby T, Johnstone KA, Resnick JL, Holland AJ, Hagan JJ, Wilkinson LS, Isles AR (2010) Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader–Willi syndrome. Eur J Neurosci 31:156–164PubMedCrossRefGoogle Scholar
  54. Ripley TL, Horwood JM, Stephens DN (2001) Evidence for impairment of behavioural inhibition in performance of operant tasks in tPA−/− mice. Behav Brain Res 125:215–227PubMedCrossRefGoogle Scholar
  55. Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl) 163:362–380CrossRefGoogle Scholar
  56. Robinson ES, Eagle DM, Economidou D, Theobald DE, Mar AC, Murphy ER, Robbins TW, Dalley JW (2009) Behavioural characterisation of high impulsivity on the 5-choice serial reaction time task: specific deficits in ‘waiting’ versus ‘stopping’. Behav Brain Res 196:310–316PubMedCrossRefGoogle Scholar
  57. Romberg C, Mattson MP, Mughal MR, Bussey TJ, Saksida LM (2011) Impaired attention in the 3xTgAD mouse model of Alzheimer’s disease: rescue by donepezil (Aricept). J Neurosci 31:3500–3507PubMedCrossRefGoogle Scholar
  58. Siegel JA, Benice TS, Van Meer P, Park BS, Raber J (2011) Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E. Neurobiol Aging 32:75–84PubMedCrossRefGoogle Scholar
  59. Stephens DN, Duka T (2008) Review. Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex. Philos Trans R Soc Lond B Biol Sci 363:3169–3179PubMedCrossRefGoogle Scholar
  60. Stephens DN, Voet B (1994) Differential effects of anxiolytic and non-anxiolytic benzodiazepine receptor ligands on performance of a differential reinforcement of low rate (DRL) schedule. Behav Pharmacol 5:4–14PubMedCrossRefGoogle Scholar
  61. van Gaalen MM, Stenzel-Poore M, Holsboer F, Steckler T (2003) Reduced attention in mice overproducing corticotropin-releasing hormone. Behav Brain Res 142:69–79PubMedCrossRefGoogle Scholar
  62. Walker SE, Peña-Oliver Y, Stephens DN (2011) Learning not to be impulsive: disruption by experience of alcohol withdrawal. Psychopharmacology (Berl) 217(3):433–442Google Scholar
  63. Winstanley CA (2007) The orbitofrontal cortex, impulsivity, and addiction: probing orbitofrontal dysfunction at the neural, neurochemical, and molecular level. Ann N Y Acad Sci 1121:639–655PubMedCrossRefGoogle Scholar
  64. Wittmann M, Paulus MP (2008) Decision making, impulsivity and time perception. Trends Cogn Sci 12:7–12PubMedCrossRefGoogle Scholar
  65. Wrenn CC, Turchi JN, Schlosser S, Dreiling JL, Stephenson DA, Crawley JN (2006) Performance of galanin transgenic mice in the 5-choice serial reaction time attentional task. Pharmacol Biochem Behav 83:428–440PubMedCrossRefGoogle Scholar
  66. Yadid G, Sudai E, Maayan R, Gispan I, Weizman A (2010) The role of dehydroepiandrosterone (DHEA) in drug-seeking behavior. Neurosci Biobehav Rev 35:303–314PubMedCrossRefGoogle Scholar
  67. Yan TC, Dudley JA, Weir RK, Grabowska EM, Peña-Oliver Y, Ripley TL, Hunt SP, Stephens DN, Stanford SC (2011) Performance deficits of NK1 receptor knockout mice in the 5-choice serial reaction-time task: effects of d-amphetamine, stress and time of day. PLoS One 6:e17586PubMedCrossRefGoogle Scholar
  68. 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 29:891–900PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sandra Sanchez-Roige
    • 1
  • Yolanda Peña-Oliver
    • 1
  • David N. Stephens
    • 1
  1. 1.School of PsychologyUniversity of SussexBrightonUK

Personalised recommendations