The Five‐Choice Continuous Performance Task (5C‐CPT): A Cross‐Species Relevant Paradigm for Assessment of Vigilance and Response Inhibition in Rodents

Zackary A. Cope1, Jared W. Young1

1 Department of Psychiatry, University of California San Diego, La Jolla, California
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.56
DOI:  10.1002/cpns.20
Online Posting Date:  January, 2017
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


Deficits in the domains of attention and response inhibition are central to many psychiatric disorders. As such, animal models of disorders purporting to replicate these behavioral deficits first require tests that can accurately assess the behaviors with high fidelity. The gold‐standard clinical test of attention and response inhibition is the continuous performance test (CPT). Although there are a number of CPTs, all share the premise of responding to target stimuli and inhibiting from responding to non‐target stimuli. The recently developed rodent five‐choice CPT (5C‐CPT) requires similar behavioral responses, enabling signal detection parameter calculations. With demonstrable feasibility for rodent testing, the 5C‐CPT permits/facilitates: (1) delineation of neural mechanisms underlying these behaviors; (2) multifactorial analyses of the complex interplay between genetic and environmental manipulations relevant to psychiatric disorders; and hence (3) development of novel targeted treatments. All data to date indicate that the rodent 5C‐CPT described here has direct translatability to clinical CPTs, producing equivalent measures of behavior in experimental animals to those assessed in humans. The 5C‐CPT task provides an important tool toward delineating these mechanisms and developing treatments. However, it is also complex, with long training times and nuances requiring a thorough understanding before utilization. This unit will enable researchers to avoid potential missteps, greatly increasing the likelihood of success. © 2017 by John Wiley & Sons, Inc.

Keywords: attention; vigilance; impulsivity; cross‐species

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Handling, Food Restriction, and Operant Chamber Habituation
  • Basic Protocol 2: 5CSRTT‐to‐5C‐CPT Shaping
  • Basic Protocol 3: 5C‐CPT Challenges
  • Commentary
  • Literature Cited
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


Basic Protocol 1: Handling, Food Restriction, and Operant Chamber Habituation

  • Rodent species of interest (see Critical Parameters; Table 9.56.1)
  • Strawberry milkshake powder (e.g., Nestle Nesquik)
  • Skim milk
  • Means for rodent identification, e.g., numbered ear tags, ear punches, tattoos, microchip transponders
  • Appropriate rodent housing facilities (see step 1 and Critical Parameters), including:
    • Standard Allentown Microvent cages with HEPA filtration
    • Rodent chow pellets (e.g., Harlan Teklad 8460) suitable for wire cage top hoppers
    • Sipper tube bottles
    • Nestlets, paper towels, chew blocks
    • Cart and drape for transporting animals
  • Digital small animal scale (e.g., Ohaus CS200)
  • Apparatus:
    • Five‐Hole Nose Poke Wall Chambers for rat (25 × 25 × 25 mm; Med Associates, product no. MED‐NP5L‐B1; see Fig.  )
    • Power Control and Interface (PCI) Operating Package (Med Associates, MED‐SYST‐16)
    • Windows XP computer (or higher capability) with PCI card installed
    • Med‐PC software package (Med Associates, SOF‐735)
    • Smart Control Interface (Med Associates, DIG‐716P2; one per chamber)
    • Med‐PC executable behavioral programs (see Fig.  )
  • Fluid reward delivery system:
    • Peristaltic pump for liquid reward (Lafayette, model 80204M)
    • Small plastic cup (∼50 ml) for each behavioral chamber (to hold ≥2 ml Nesquik reward per animal throughout the day)
  • Cleaning materials:
    • Large lint‐free tissues (e.g., Kimtech Kimwipes)
    • 60% (v/v) ethanol
    • Disinfectant spray (e.g., Airx 44)
  • Personal protection equipment:
    • N‐95 Mask
    • Disposable gloves
    • Lab coat or disposable coveralls
Table 9.6.1   MaterialsVerified Rat and Mouse Strains for the 5C‐CPT

Species Strain Identifier/reference
Rats Long‐Evans RRID:RGD_2308852
Inbred mice C57BL/6J RRID:IMSR_JAX:000664
129S1/SvImJ RRID:IMSR_JAX:002448
In‐house mutant mice D4 heterozygotes (DRD4) Young et al. (2011)
Dopamine transporter (DAT) hypomorphs (DAT‐HY)
Specificity Protein 4 (SP4) hypomorphs Young et al. (2011)

PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
  Barch, D.M. and Carter, C.S. 2008. Measurement issues in the use of cognitive neuroscience tasks in drug development for impaired cognition in schizophrenia: A report of the Second Consensus Building Conference of the CNTRICS Initiative. Schizophr Bull 34(4):613‐618. doi: 10.1093/schbul/sbn037.
  Barnes, S.A., Young, J.W., and Neill, J.C. 2012. 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 62:1432‐1441. doi: 10.1016/j.neuropharm.2011.04.024.
  Beck, L.H., Bransome, E.D. Jr., Mirsky, A.F., Rosvold, H.E., and Sarason, I. 1956. A continuous performance test of brain damage. J. Consult. Psychol. 20:343‐350. doi: 10.1037/h0039381.
  Conners, C.K. 1985. The computerized continuous performance test. Psychopharmacol. Bull. 21:891‐892.
  Cope, Z.A., Halberstadt, A.L., van Enkhuizen, J., Flynn, A.D., Breier, M., Swerdlow, N.R., Geyer, M.A., and Young, J.W. 2016. Premature responses in the five‐choice serial reaction time task reflect rodents’ temporal strategies: Evidence from no‐light and pharmacological challenges. Psychopharmacology (Berl) 233:3513‐3525. doi: 10.1007/s00213‐016‐4389‐4.
  Dudchenko, P.A., Talpos, J., Young, J., and Baxter, M.G. 2013. Animal models of working memory: A review of tasks that might be used in screening drug treatments for the memory impairments found in schizophrenia. Neurosci. Biobehav. Rev. 37:2111‐2124. doi: 10.1016/j.neubiorev.2012.03.003.
  Fletcher, P.J., Tampakeras, M., Sinyard, J., and Higgins, G.A. 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) 195:223‐234. doi: 10.1007/s00213‐007‐0891‐z.
  Floresco, S.B., Geyer, M.A., Gold, L.H., and Grace, A.A. 2005. Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia. Schizophr. Bull. 31:888‐894. doi: 10.1093/schbul/sbi041.
  Geyer, M.A., Olivier, B., Joels, M., and Kahn, R.S. 2012. From antipsychotic to anti‐schizophrenia drugs: Role of animal models. Trends Pharmacol. Sci. 33:515‐521. doi: 10.1016/
  Gilmour, G., Arguello, A., Bari, A., Brown, V.J., Carter, C., Floresco, S.B., Jentsch, D.J., Tait, D.S., Young, J.W., and Robbins, T.W. 2013. Measuring the construct of executive control in schizophrenia: Defining and validating translational animal paradigms for discovery research. Neurosci. Biobehav. Rev. 37:2125‐2140. doi: 10.1016/j.neubiorev.2012.04.006.
  Goldberg, J.F. and Chengappa, K.N. 2009. Identifying and treating cognitive impairment in bipolar disorder. Bipolar Disord. 2:123‐137. doi: 10.1111/j.1399‐5618.2009.00716.x.
  Green, M.F., Nuechterlein, K.H., Kern, R.S., Baade, L.E., Fenton, W.S., Gold, J.M., Keefe, R.S., Mesholam‐Gately, R., Seidman, L.J., Stover, E., and Marder, S.R. 2008. Functional co‐primary measures for clinical trials in schizophrenia: Results from the MATRICS Psychometric and Standardization Study. Am. J. Psychiatry 165:221‐228. doi: 10.1176/appi.ajp.2007.07010089.
  Humby, T., Wilkinson, L., and Dawson, G. 2005. Assaying aspects of attention and impulse control in mice using the 5‐choice serial reaction time task. Curr. Protoc. Neurosci. 31:8.5H.1‐8.5H.15. doi: 10.1002/0471142301.ns0805hs31.
  Lustig, C., Kozak, R., Sarter, M., Young, J.W., and Robbins, T.W. 2013. CNTRICS final animal model task selection: Control of attention. Neurosci. Biobehav. Rev. 37:2099‐2110. doi: 10.1016/j.neubiorev.2012.05.009.
  MacDonald, A.W. 3rd. 2008. Building a clinically relevant cognitive task: Case study of the AX paradigm. Schizophr. Bull. 34:619‐628. doi: 10.1093/schbul/sbn038.
  McKenna, B.S., Young, J.W., Dawes, S.E., Asgaard, G.L., and Eyler, L.T. 2013. Bridging the bench to bedside gap: Validation of a reverse‐translated rodent continuous performance test using functional magnetic resonance imaging. Psychiatry Res. 212:183‐191. doi: 10.1016/j.pscychresns.2013.01.005.
  Moore, H., Geyer, M.A., Carter, C.S., and Barch, D.M. 2013. Harnessing cognitive neuroscience to develop new treatments for improving cognition in schizophrenia: CNTRICS selected cognitive paradigms for animal models. Neurosci. Biobehav. Rev. 37:2087‐2091. doi: 10.1016/j.neubiorev.2013.09.011.
  Porter, A.J., Pillidge, K., Stanford, S.C., and Young, J.W. 2016. Differences in the performance of NK1R‐/‐ ('knockout') and wildtype mice in the 5‐Choice Continuous Performance Test. Behav. Brain Res. 298:268‐277. doi: 10.1016/j.bbr.2015.10.045.
  Riccio, C.A., Waldrop, J.J., Reynolds, C.R., and Lowe, P. 2001. Effects of stimulants on the continuous performance test (CPT): Implications for CPT use and interpretation. J. Neuropsychiatry Clin. Neurosci. 13(3):326‐335. doi: 10.1176/jnp.13.3.326.
  Sarter, M. 2004. Animal cognition: Defining the issues. Neurosci. Biobehav. Rev. 28:645‐650. doi: 10.1016/j.neubiorev.2004.09.005.
  Spratt, C., McQuatt, N.E., Sharkey, J., Kelly, J.S., and Marston, H.M. 2001. Comparison of rats and mice in a serial reaction task. British Neuroscience Association, U.K., Abstracts 16.
  van Enkhuizen, J., Acheson, D., Risbrough, V., Drummond, S., Geyer, M.A., and Young, J.W. 2014. Sleep deprivation impairs performance in the 5‐choice continuous performance test: Similarities between humans and mice. Behav. Brain Res. 261:40‐48. doi: 10.1016/j.bbr.2013.12.003.
  Young, J.W. and Geyer, M.A. 2015. Developing treatments for cognitive deficits in schizophrenia: The challenge of translation. J. Psychopharmacol. 29:178‐196.
  Young, J.W. and Markou, A. 2015. Translational rodent paradigms to investigate neuromechanisms underlying behaviors relevant to amotivation and altered reward processing in schizophrenia. Schizophr. Bull. 41:1024‐1034.
  Young, J.W., Light, G.A., Marston, H.M., Sharp, R., and Geyer, M.A. 2009. The 5‐choice continuous performance test: Evidence for a translational test of vigilance for mice. PLoS One 4:e4227. doi: 10.1371/journal.pone.0004227.
  Young, J.W., Powell, S.B., Scott, C.N., Zhou, X., and Geyer, M.A. 2011. 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. doi: 10.1016/j.bbr.2011.03.054.
  Young, J.W., Jentsch, J.D., Bussey, T.J., Wallace, T.L., and Hutcheson, D.M. 2013a. Consideration of species differences in developing novel molecules as cognition enhancers. Neurosci. Biobehav. Rev. 37:2181‐2193. doi: 10.1016/j.neubiorev.2012.10.002.
  Young, J.W., Geyer, M.A., Rissling, A.J., Sharp, R.F., Eyler, L.T., Asgaard, G.L., and Light, G.A. 2013b. Reverse translation of the rodent 5C‐CPT reveals that the impaired attention of people with schizophrenia is similar to scopolamine‐induced deficits in mice. Transl. Psychiatry 3:e324. doi: 10.1038/tp.2013.82.
  Young, J.W., Kamenski, M.E., Higa, K.K., Light, G.A., Geyer, M.A., and Zhou, X. 2015. GlyT‐1 inhibition attenuates attentional but not learning or motivational deficits of the Sp4 hypomorphic mouse model relevant to psychiatric disorders. Neuropsychopharmacology 40:2715‐2726. doi: 10.1038/npp.2015.120.
PDF or HTML at Wiley Online Library