Investigating Affective Bias in Mice Using A Novel Operant Task

Abstract

Cognitive affective bias has been highlighted as a key feature in Major Depressive Disorder (MDD). Specifically, judgement bias has been successfully measured in animals, in regards to their welfare, and has also shown promise in MDD research. This study aimed to investigate a mouse version of a rat judgement bias task (JBT) which has shown pharmacological sensitivity to acute rapid-acting antidepressants. The initial pilot study, behavioral task 1, trained the mice with the same protocol and progression criterion as rats but this task failed to achieve mice which could accurately discriminate the tones. Revisions were made to the protocol based on the findings of behavioral task 1. A new protocol was used for behavioral task 2 which successfully trained the mice in this tone-based judgement bias paradigm. The cognitive bias index (CBI) of individual mice and as a group were calculated in the probe sessions, resulting in a neutral group CBI while the individual mice CBI were spread across the spectrum from -1 to +1. Following the probe sessions, an explorative study assessing the response and sensitivity of several known pharmacological modulators of affective state were carried out. The acute pharmacology studies were based on compounds (amphetamine, ketamine and FG7142) previously used in the rat task and shown to induce positive and negative shifts in judgement bias. The results of the pharmacology study found that mice did not respond in the same way as rats; clear conclusions were difficult to draw due to the low number of animals for the studies resulting in a low statistical power. The results of both training, probe sessions and pharmacology studies has shown a difference in reward valuation when compared to the rat’s data. Rats show a clear preference for the high reward tone in their response latency during training stages while mice fail to show this preference during training. However, towards the end of the pharmacology studies, there appeared to be a preference for the high reward seen in the omission data. The behavioral differences between mice and rats highlighted in this task raise the need for further investigations and also support repetition of behavioral task 2’s protocol with a larger number of animals for subsequent pharmacology studies.

Date of Award	23 Mar 2021
Original language	English
Awarding Institution	University of Bristol
Supervisor	Emma S J Robinson (Supervisor) & Claire A Hales (Supervisor)