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Updated: Dec 17, 2025
An Automated T-maze Based Apparatus and Protocol for Analyzing Delay- and Effort-based Decision Making in Free Moving Rodents
Published on: August 2, 2018
The dopamine depleting agent tetrabenazine alters effort-related decision making as assessed by mouse touchscreen
Jen-Hau Yang1, Rose E Presby1, Renee A Rotolo1
1Behavioral Neuroscience Division, Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
Rationale:
Effort-based decision-making tasks allow animals to choose between preferred reinforcers that require high effort to obtain vs. low-effort/low reward options. Mesolimbic dopamine (DA) and related neural systems regulate effort-based choice. Tetrabenazine (TBZ) is a vesicular monoamine transport type-2 inhibitor that blocks DA storage and depletes DA. In humans, TBZ induces motivational dysfunction and depression. TBZ has been shown reliably to induce a low-effort bias in rats, but there are fewer mouse studies.
Objectives:
The present studies used touchscreen operant procedures (Bussey-Saksida chambers) to assess the effects of TBZ on effort-based choice in mice.
Methods:
C57BL6 mice were trained to press an elevated lit panel on the touchscreen on a fixed ratio 1 schedule reinforced by strawberry milkshake, vs. approaching and consuming a concurrently available but less preferred food pellets (Bio-serv).
Results:
TBZ (2.0-8.0 mg/kg IP) shifted choice, producing a dose-related decrease in panel pressing but an increase in pellet intake. In contrast, reinforcer devaluation by pre-feeding substantially decreased both panel pressing and pellet intake. In free-feeding choice tests, mice strongly preferred the milkshake vs. the pellets, and TBZ had no effect on milkshake intake or preference, indicating that the TBZ-induced low-effort bias was not due to changes in primary food motivation or preference. TBZ significantly decreased tissue levels of nucleus accumbens DA.
Conclusion:
The DA depleting agent TBZ induced an effort-related motivational dysfunction in mice, which may have clinical relevance for assessing novel drug targets for their potential use as therapeutic agents in patients with motivation impairments.
