Optimizing reproducibility of operant testing through reinforcer standardization: Identification of key nutritional constituents determining reward strength in touchscreens

Eun Woo Kim, Benjamin U. Phillips, Christopher J. Heath, So Yeon Cho, Hyunjeong Kim, Jemeen Sreedharan, Ho Taek Song, Jong Eun Lee, Timothy J. Bussey, Chul Hoon Kim, Eosu Kim, Lisa M. Saksida

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Reliable and reproducible assessment of animal learning and behavior is a central aim of basic and translational neuroscience research. Recent developments in automated operant chamber technology have led to the possibility of universal standard protocols, in addition to increased translational potential, reliability and accuracy. However, the impact of regional and national differences in the supplies of available reinforcers in this system on behavioural performance and inter-laboratory variability is an unknown and at present uncontrolled variable. Therefore, we aimed to identify which constituent(s) of the reward determines reinforcer strength to enable improved standardization of this parameter across laboratories. Male C57BL/6 mice were examined in the touchscreen-based fixed ratio (FR) and progressive ratio (PR) schedules, reinforced with different kinds of milk-based reinforcers to directly compare the incentive values of plain milk (PM, high-calorie: high-fat/low-sugar), strawberry-flavored milk (SM, high-calorie: low-fat/high-sugar), and semi-skimmed low-fat milk (LM, low-calorie: low-fat/low-sugar) on the basis of differences in caloric content, sugar/fat content, and flavor. Use of a higher caloric content reward was effective in increasing operant training acquisition rate. Total trial number completed in FR and breakpoint in PR were higher using the two isocaloric milk products (PM and SM) than the lower caloric LM, with comparable outcomes between PM and SM conditions, suggesting that total caloric content determines reward strength. Analysis of within-session changes in response rate revealed that overall outputs in FR and PR primarily depend on the response rate at the initial phase of a session, which itself was dependent on reinforcer caloric content. Interestingly, the rate of satiation, indicated by decay in response rate within a FR session, was highest when reinforced with SM, suggesting a rapid satiating effect of sugar. The key contribution of reward caloric content to operant performance was confirmed in a multi-laboratory study using the touchscreen 5-choice serial reaction time task (5-CSRTT) reinforced by two isocaloric milk-based liquid rewards with different countries of origin, which yielded consistent performance parameters across sites. Our results indicate that milk-based liquid reinforcer standardization can be facilitated by matching caloric content across laboratories despite regional or national differences in other non-caloric aspects of the reinforcers.

Original languageEnglish
Article number31
JournalMolecular brain
Issue number1
Publication statusPublished - 2017 Jul 17

Bibliographical note

Funding Information:
This study was supported by a grant from the Korean Health Technology R&D Project (HI14C2173), Ministry of Health and Welfare, Republic of Korea. BUP is supported by a Medical Research Council Ph.D. Studentship. CJH, TJB and LMS are supported by a Project Grant from the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC/N001451/1).

Publisher Copyright:
© 2017 The Author(s).

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Optimizing reproducibility of operant testing through reinforcer standardization: Identification of key nutritional constituents determining reward strength in touchscreens'. Together they form a unique fingerprint.

Cite this