NC3Rs | 20 Years: Pioneering Better Science
Project grant

Development and validation of a rodent touchscreen battery for assessing motivation and affective state

Blue pipette tips

At a glance

Completed
Award date
April 2016 - April 2018
Grant amount
£350,694
Principal investigator
Dr Lisa Saksida

Co-investigator(s)

Institute
University of Cambridge

R

  • Refinement
Read the abstract
View the grant profile on GtR

Contents

Application abstract

Motivation and emotional processing are compromised in numerous disorders (e.g., Alzheimer's disease, schizophrenia and depression) and thus are frequently assessed in rodent disease models. However, most current tests fall into the moderate severity band as they are highly aversive and involve restraint, inescapable electric shock or forced swimming. The rodent touchscreen testing system is well-established as a versatile cognitive assessment tool that avoids aversive conditions, instead using rewards such as milkshake.

We propose to develop a suite of rodent touchscreen-based assays for motivation and emotion and show that they can replace higher-severity assays (refinement) by validating their efficacy with a series of experiments focused on three manipulations known to affect different aspects of these constructs: (I) a standardised panel of drugs; (II) chronic exposure to the stress hormone corticosterone; and (III) ethologically-valid environmental manipulations. This will also demonstrate the utility of these tasks for assessing new drugs for benefits on emotional state, for measuring rodent stress and monitoring welfare, and for standardised assessment of new welfare manipulations such as environmental enrichment or changes in husbandry practises. 

Aversive tasks to measure emotion and motivation are used extensively. Widespread adoption of touchscreen-based assays to assess emotion and motivation could decrease the severity of testing for at least 30,000 rodents annually. Touchscreen-based rodent tests are very similar to those used in humans, which greatly increases the probability of successful translation of treatments from the lab to the clinic, potentially reducing the number of animal experiments required. Additional advantages are increased precision of data through automation and computerisation and the possibility of conducting multiple tests in the same apparatus, both of which contribute to reduction.

Impacts

Publications

  1. Lopez-Cruz et al. (2021). Using touchscreen-delivered cognitive assessments to address the principles of the 3Rs in behavioral sciences. Lab Animal doi: 10.1038/s41684-021-00791-2
  2. Heath CJ et al. (2019). A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice. Frontiers in Neurology 10:858. doi: 10.3389/fneur.2019.00858
  3. Lim J et al. (2019). Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses. Molecular Brain 12:37. doi: 10.1186/s13041-019-0441-8
  4. Phillips BU et al. (2019). Translational tests involving non-reward: methodological considerations. Psychopharmacology 236(1):449-461. doi: 10.1007/s00213-018-5062-x
  5. Aitta-Aho T et al. (2018). Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala Circuits and Learning-Related Behavior. Current biology 28(16):2557-2569. doi: 10.1016/j.cub.2018.06.064
  6. Hailwood JM et al. (2018). Blockade of muscarinic acetylcholine receptors facilitates motivated behaviour and rescues a model of antipsychotic-induced amotivation. Neuropsychopharmacology 44(6):1068-1075. doi: 10.1038/s41386-018-0281-8
  7. Hailwood JM et al. (2018). Validation and optimisation of a touchscreen progressive ratio test of motivation in male rats. Psychopharmacology 235(9):2739-2753. doi: 10.1007/s00213-018-4969-6
  8. Phillips BU et al. (2018). Translational approaches to evaluating motivation in laboratory rodents: conventional and touchscreen-based procedures. Current Opinion in Behavioral Sciences 22:21-27 doi: 10.1016/j.cobeha.2017.12.008
  9. Phillips BU et al. (2018). Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice. Psychopharmacology 235(7):2101-11. doi: 10.1007/s00213-018-4907-7
  10. White MA et al. (2018). TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD. Nature Neuroscience 21(4):552-563. doi: 10.1038/s41593-018-0113-5
  11. Kim EW et al. (2017). Optimizing reproducibility of operant testing through reinforcer standardization: identification of key nutritional constituents determining reward strength in touchscreens. Mol Brain 10(1):31. doi: 10.1186/s13041-017-0312-0
  12. Phillips BU et al. (2017).  Optimisation of cognitive performance in rodent operant (touchscreen) testing: Evaluation and effects of reinforcer strength. Learning and Behavior 45(3):252-262. doi: 10.3758/s13420-017-0260-7