Measuring Motivation and Reward‐Related Decision Making in the Rodent Operant Touchscreen System

Christopher J. Heath1, Benjamin U. Phillips1, Timothy J. Bussey1, Lisa M. Saksida1

1 Department of Psychology and MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 8.34
DOI:  10.1002/0471142301.ns0834s74
Online Posting Date:  January, 2016
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

This unit is designed to facilitate implementation of the fixed and progressive ratio paradigms and the effort‐related choice task in the rodent touchscreen apparatus to permit direct measurement of motivation and reward‐related decision making in this equipment. These protocols have been optimized for use in the mouse and reliably yield stable performance levels that can be enhanced or suppressed by systemic pharmacological manipulation. Instructions are also provided for the adjustment of task parameters to permit use in mouse models of neurodegenerative disease. These tasks expand the utility of the rodent touchscreen apparatus beyond the currently available battery of cognitive assessment paradigms. © 2016 by John Wiley & Sons, Inc.

Keywords: touchscreen; motivation; effort‐related choice; mouse

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Initial Handling, Food Restriction, and Operant Chamber Acclimatization
  • Alternate Protocol 1: Initial Handling, Food Restriction, and Operant Chamber Acclimatization Adapted for Progressive Neurodegenerative Mouse Models
  • Basic Protocol 2: Assessment of Mouse Motivation using the Touchscreen Progressive Ratio Task
  • Alternate Protocol 2: Assessment of Motivation using the Touchscreen Progressive Ratio Task Adapted for Mouse Models of Progressive Neurodegenerative Disease
  • Basic Protocol 3: Evaluation of Reward‐Related Decision Making in the Mouse using the Touchscreen Version of the Effort‐Related Choice Task
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Initial Handling, Food Restriction, and Operant Chamber Acclimatization

  Materials
  • Rodents of interest (see Critical Parameters)
  • Rodent housing environment (see Critical Parameters)
    • Drinking water
    • Standard rodent food (e.g., Diet RM 3, Special Diet Services)
  • Food rewards (pellets or milkshake) with appropriate dispensing system (pellet hopper or liquid reservoir)
  • Rodent housing facility (see Critical Parameters)
    • Bedding
    • Shelter
    • Environmental enrichment (e.g., chew blocks)
  • Equipment for rodent identification (see appendix 4E)
  • Scale (for weighing rodents)
  • Behavioral chambers
  • Rodent touchscreen system (see Critical Parameters)
  • Cleaning materials
    • Disinfectant spray (e.g., Distel High Level Laboratory Disinfectant, Tristel Solutions)
    • Cleaning brush
    • Filter paper waste tray liners
  • Personal protection equipment
    • FFP2 mask/respirator
    • Disposable gloves
    • Coveralls

Alternate Protocol 1: Initial Handling, Food Restriction, and Operant Chamber Acclimatization Adapted for Progressive Neurodegenerative Mouse Models

  Additional Materials (see also protocol 1)
  • Moistened standard rodent food
  • Liquid reward

Basic Protocol 2: Assessment of Mouse Motivation using the Touchscreen Progressive Ratio Task

  Materials
  • Rodents of interest (see Critical Parameters)
  • Rodent housing environment (see Critical Parameters)
    • Drinking water
    • Standard rodent food (e.g., Diet RM 3, Special Diet Services)
  • Food rewards (pellets or milkshake) with appropriate dispensing system (pellet hopper or liquid reservoir)
  • Rodent housing facility (see Critical Parameters)
    • Bedding
    • Shelter
    • Environmental enrichment (e.g., chew blocks)
  • Scale (for weighing rodents)
  • Behavioral chambers
  • Rodent touchscreen system (see Critical Parameters)
  • Cleaning materials
    • Disinfectant spray (e.g., Distel High Level Laboratory Disinfectant, Tristel Solutions)
    • Cleaning brush
    • Filter paper waste tray liners
  • Personal protection equipment
    • FFP2 mask/respirator
    • Disposable gloves
    • Coveralls

Alternate Protocol 2: Assessment of Motivation using the Touchscreen Progressive Ratio Task Adapted for Mouse Models of Progressive Neurodegenerative Disease

  Additional Materials (see also protocol 3)
  • Moistened standard rodent food
  • Liquid reward

Basic Protocol 3: Evaluation of Reward‐Related Decision Making in the Mouse using the Touchscreen Version of the Effort‐Related Choice Task

  Materials
  • Rodents of interest (see Critical Parameters)
  • Rodent housing environment (see Critical Parameters)
    • Drinking water
    • Standard rodent food (e.g., Diet RM 3, Special Diet Services)
  • Food rewards (pellets or milkshake) with appropriate dispensing system (pellet hopper or liquid reservoir)
  • Rodent housing facility (see Critical Parameters)
    • Bedding
    • Shelter
    • Environmental enrichment (e.g., chew blocks)
  • Scale (for weighing rodents)
  • Behavioral chambers
  • Rodent touchscreen system (see Critical Parameters)
  • Cleaning materials
    • Disinfectant spray (e.g., Distel High Level Laboratory Disinfectant, Tristel Solutions)
    • Cleaning brush
    • Filter paper waste tray liners
  • Personal protection equipment
    • FFP2 mask/respirator
    • Disposable gloves
    • Coveralls
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
  Aberman, J.E., Ward, S.J., and Salamone, J.D. 1998. Effects of dopamine antagonists and accumbens dopamine depletions on time‐constrained progressive‐ratio performance. Pharmacol. Biochem. Behav. 61:341‐348. doi: 10.1016/S0091-3057(98)00112-9.
  Beeler, J.A., Prendergast, B., and Zhuang, X. 2006. Low amplitude entrainment of mice and the impact of circadian phase on behavior tests. Physiol. Behav. 87:870‐880. doi: 10.1016/j.physbeh.2006.01.037.
  Bensadoun, J.‐C., Brooks, S.P., and Dunnett, S.B. 2004. Free operant and discrete trial performance of mice in the nine‐hole box apparatus: Validation using amphetamine and scopolamine. Psychopharmacology 174:396‐405. doi: 10.1007/s00213-003-1751-0.
  Bussey, T.J., Holmes, A., Lyon, L., Mar, A.C., McAllister, K.A.L., Nithianantharajah, J., Oomen, C.A., and Saksida, L.M. 2012. New translational assays for preclinical modelling of cognition in schizophrenia: The touchscreen testing method for mice and rats. Neuropharmacology 62:1191‐1203. doi: 10.1016/j.neuropharm.2011.04.011.
  Chaudhury, D. and Colwell, C.S. 2002. Circadian modulation of learning and memory in fear‐conditioned mice. Behav. Brain Res. 133:95‐108. doi: 10.1016/S0166-4328(01)00471-5.
  Creer, D.J., Romberg, C., Saksida, L.M., van Praag, H., and Bussey, T.J. 2010. Running enhances spatial pattern separation in mice. Proc. Natl. Acad. Sci. U.S.A. 107:2367‐2372. doi: 10.1073/pnas.0911725107.
  Drew, M.R., Simpson, E.H., Kellendonk, C., Herzberg, W.G., Lipatova, O., Fairhurst, S., Kandel, E.R., Malapani, C., and Balsam, P.D. 2007. Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. J. Neurosci. 27:7731‐7739. doi: 10.1523/JNEUROSCI.1736-07.2007.
  Frick, K.M. and Berger‐Sweeney, J. 2001. Spatial reference memory and neocortical neurochemistry vary with the estrous cycle in C57BL/6 mice. Behav. Neurosci. 115:229‐237. doi: 10.1037/0735-7044.115.1.229.
  Gourley, S.L., Lee, A.S., Howell, J.L., Pittenger, C., and Taylor, J.R. 2010. Dissociable regulation of instrumental action within mouse prefrontal cortex. Eur. J. Neurosci. 32:1726‐1734. doi: 10.1111/j.1460-9568.2010.07438.x.
  Gourley, S.L., Wu, F.J., Kiraly, D.D., Ploski, J.E., Kedves, A.T., Duman, R.S., and Taylor, J.R. 2008. Regionally specific regulation of ERK MAP kinase in a model of antidepressant‐sensitive chronic depression. Biol. Psychiatry 63:353‐359. doi: 10.1016/j.biopsych.2007.07.016.
  Heath, C.J., Bussey, T.J., and Saksida, L.M. 2015. Motivational assessment of mice using the touchscreen operant testing system: Effects of dopaminergic drugs. Psychopharmacology ePub ahead of print.
  Hodos, W. 1961. Progressive ratio as a measure of reward strength. Science 134:943‐944. doi: 10.1126/science.134.3483.943.
  Horner, A.E., Heath, C.J., Hvoslef‐Eide, M., Kent, B.A., Kim, C.H., Nilsson, S.R.O., Alsiö, J., Oomen, C.A., Holmes, A., Saksida, L.M., and Bussey, T.J. 2013. The touchscreen operant platform for testing learning and memory in rats and mice. Nat. Protoc. 8:1961‐1984. doi: 10.1038/nprot.2013.122.
  Mar, A.C., Horner, A.E., Nilsson, S.R.O., Alsiö, J., Kent, B.A., Kim, C.H., Holmes, A., Saksida, L.M., and Bussey, T.J. 2013. The touchscreen operant platform for assessing executive function in rats and mice. Nat. Protoc. 8:1985‐2005. doi: 10.1038/nprot.2013.123.
  Markou, A., Salamone, J.D., Bussey, T.J., Mar, A.C., Brunner, D., Gilmour, G., and Balsam, P. 2013. Measuring reinforcement learning and motivation constructs in experimental animals: Relevance to the negative symptoms of schizophrenia. Neurosci. Biobehav. Rev. 37:2149‐2165. doi: 10.1016/j.neubiorev.2013.08.007.
  Meziane, H., Ouagazzal, A.‐M., Aubert, L., Wietrzych, M., and Krezel, W. 2007. Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: Implications for phenotyping strategies. Genes Brain Behav. 6:192‐200. doi: 10.1111/j.1601-183X.2006.00249.x.
  Nunes, E.J., Randall, P.A., Hart, E.E., Freeland, C., Yohn, S.E., Baqi, Y., Müller, C.E., López‐Cruz, L., Correa, M., and Salamone, J.D. 2013a. Effort‐related motivational effects of the VMAT‐2 inhibitor tetrabenazine: Implications for animal models of the motivational symptoms of depression. J. Neurosci. 33:19120‐19130. doi: 10.1523/JNEUROSCI.2730-13.2013.
  Nunes, E.J., Randall, P.A., Podurgiel, S., Correa, M., and Salamone, J.D. 2013b. Nucleus accumbens neurotransmission and effort‐related choice behavior in food motivation: Effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors. Neurosci. Biobehav. Rev. 37:2015‐2025. doi: 10.1016/j.neubiorev.2013.04.002.
  Olausson, P., Kiraly, D.D., Gourley, S.L., and Taylor, J.R. 2013. Persistent effects of prior chronic exposure to corticosterone on reward‐related learning and motivation in rodents. Psychopharmacology 225:569‐577. doi: 10.1007/s00213-012-2844-4.
  Oomen, C.A., Hvoslef‐Eide, M., Heath, C.J., Mar, A.C., Horner, A.E., Bussey, T.J., and Saksida, L.M. 2013. The touchscreen operant platform for testing working memory and pattern separation in rats and mice. Nat. Protoc. 8:2006‐2021. doi: 10.1038/nprot.2013.124.
  Pardo, M., Lopez‐Cruz, L., Valverde, O., Ledent, C., Baqi, Y., Müller, C.E., Salamone, J.D., and Correa, M. 2012. Adenosine A2A receptor antagonism and genetic deletion attenuate the effects of dopamine D2 antagonism on effort‐based decision making in mice. Neuropharmacology 62:2068‐2077. doi: 10.1016/j.neuropharm.2011.12.033.
  Roedel, A., Storch, C., Holsboer, F., and Ohl, F. 2006. Effects of light or dark phase testing on behavioural and cognitive performance in DBA mice. Lab. Anim. 40:371‐381. doi: 10.1258/002367706778476343.
  Salamone, J.D., Correa, M., Nunes, E.J., Randall, P.A., and Pardo, M. 2012. The behavioral pharmacology of effort‐related choice behavior: Dopamine, adenosine and beyond. J. Exp. Anal. Behav. 97:125‐146. doi: 10.1901/jeab.2012.97-125.
  Salamone, J.D., Steinpreis, R.E., McCullough, L.D., Smith, P., Grebel, D., and Mahan, K. 1991. Haloperidol and nucleus accumbens dopamine depletion suppress lever pressing for food but increase free food consumption in a novel food choice procedure. Psychopharmacology 104:515‐521. doi: 10.1007/BF02245659.
  Sharma, S., Hryhorczuk, C., and Fulton, S. 2012. Progressive‐ratio responding for palatable high‐fat and high‐sugar food in mice. J. Vis. Exp. 63:e3754. doi: 10.3791/3754.
  Trifilieff, P., Feng, B., Urizar, E., Winiger, V., Ward, R.D., Taylor, K.M., Martinez, D., Moore, H., Balsam, P.D., Simpson, E.H., and Javitch, J.A. 2013. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol. Psychiatry 18:1025‐1033. doi: 10.1038/mp.2013.57.
  Ward, R.D., Simpson, E.H., Richards, V.L., Deo, G., Taylor, K., Glendinning, J.I., Kandel, E.R., and Balsam, P.D. 2012. Dissociation of hedonic reaction to reward and incentive motivation in an animal model of the negative symptoms of schizophrenia. Neuropsychopharmacology 37:1699‐1707. doi: 10.1038/npp.2012.15.
  Wolf, J.E., Urbano, C.M., Ruprecht, C.M., and Leising, K.J. 2014. Need to train your rat? There is an App for that: A touchscreen behavioral evaluation system. Behav. Res. Methods 46:206‐214. doi: 10.3758/s13428-013-0366-6.
  Young, J.W., Meves, J.M., Tarantino, I.S., Caldwell, S., and Geyer, M.A. 2011. Delayed procedural learning in α7‐nicotinic acetylcholine receptor knockout mice. Genes Brain Behav. 10:720‐733. doi: 10.1111/j.1601-183X.2011.00711.x.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library