Measuring Motivation Using the Progressive Ratio Task in Adolescent Mice

Abstract

Alterations in reward seeking are a hallmark of multiple psychiatric disorders, including substance abuse and depression. One important aspect of reward seeking is 'wanting', which can be operationalized in both humans and rodents in tasks such as the progressive ratio, in which an increasing amount of work is required to earn a given reward. Importantly, many disorders with reward-seeking deficits are believed to have an important neurodevelopmental component, underscoring the importance of being able to study changes in motivation across the lifespan. Although this task has been adapted for both adult and adolescent rats, in mice it has predominantly been used to assay motivational changes in adults. Specific concerns in adapting this task from adult to adolescent mice include (1) optimizing a food restriction paradigm suitable for growing animals whose weights are naturally dynamically changing and (2) identifying task conditions that allow younger, smaller mice to perform the task while minimizing the length of the behavioral shaping required to measure motivation at specific developmental dates. Toward that end, we now report a protocol for appropriate weight management in developing animals that require food restriction, and a protocol for behavioral shaping and progressive ratio testing in adolescent mice, including an assessment of whether the animals perform better with lever presses or nose pokes as the required operant response. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Food restriction and weight management in the context of developing mice Alternate Protocol: Food restriction and weight management of developing mice without projected growth chart: Utilization of baseline mice Basic Protocol 2: Operant box design, progressive ratio training, testing, and data analysis in adolescent mice.

Keywords: adolescence; food restriction; mice; motivation; progressive ratio.

Figure 1.. No differences between lever presses and nose pokes on task output variables across training days.

The number of (a) total presses/pokes, (b) rewards retrieved, (c) press/poke rate, (d) session time, (e) latency to retrieve reward, and (f) latency to initiate a session did not differ between adolescent animals required to make a lever press or a nose poke across the training days.

Figure 2.. No differences between lever presses and nose pokes on PR task output variables.

The (a) breakpoint, as well as the number of (b) total presses/pokes, (c) rewards retrieved, (d) press/poke rate, (e) session time, (f) latency to retrieve reward, and (g) latency to initiate a session did not differ between adolescent animals required to make a lever press or a nose poke across the three progressive ratio test days.

Figure 3.. Progressive ratio session averages and by trial assessments track small differences in lever pressing and nose pokes.

The averaged (a) breakpoint, (b) total presses/pokes, (c) rewards retrieved, (d) press/poke rate by trial, (e) press/poke rate, (f) session time, (g) latency to retrieve the reward, (h) latency to initiate a session, and (i) latency to initiate a session by trial did not significantly differ between adolescent animals required to make a lever press or a nose poke across the three progressive ratio test days nor within most trials in PR.