Exploring different models of effort-based tasks to measure motivational states in mice

Abstract

Apathy is characterised by motivational deficits and emotional blunting, which are symptoms shared across many neuropsychiatric conditions. Although selective serotonin reuptake inhibitors
(SSRIs) are widely prescribed for major depressive disorder, they are also used to treat apathy
despite key differences between these conditions. However, growing evidence suggests SSRIs may
worsen motivational symptoms, leading to 'SSRI-induced apathy'. In preclinical research, motivation is typically assessed through goal-directed behaviour in effort-based tasks. We first investigated the operant-based Effort for Reward (EfR) task in mice, focusing on dopamine, a key
neurotransmitter in motivation, and compared our findings to rat studies. We then explored the
impact of acute SSRI administration (citalopram and escitalopram) on motivation using the EfR task.
Previous work in the lab showed different effects on motivational tasks from acute to chronic treatment using SSRI escitalopram. To compliment this, we also assessed chronic venlafaxine, a
serotonin-norepinephrine reuptake inhibitor (SNRI) and potential alternative antidepressant, on
both the EfR and the ethologically relevant, non-food motivated Effort-Based Foraging (EBF) task.
Our results revealed differences in motivated behaviours between the two tasks and between acute
versus chronic drug administration. Acute SSRI treatment increased high-effort trials in the EfR task, while chronic venlafaxine had no significant effect on motivation in the EfR and EBF tasks but was associated with blunted emotional reactivity in a modified EBF paradigm. Additionally, chronic
venlafaxine did not affect anxiety levels in the novelty-suppressed feeding test. To address
differences between the EfR and EBF tasks, we conducted a pilot study on a novel Dual Effort Choice task, which offers a multidimensional approach to studying motivation by integrating both
reinforcement-based and spontaneous behaviours. This approach may provide a more
comprehensive understanding of motivation and its modulation by pharmacological treatments.

Date of Award	10 Dec 2024
Original language	English
Awarding Institution	University of Bristol
Supervisor	Emma S J Robinson (Supervisor) & Megan G Jackson (Supervisor)