Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Bussey, Timothy J.

2nd Supervisor

Saksida, Lisa M.

Abstract

Cognitive judgement bias (CJB) refers to the interpretation of ambiguous stimuli in a negative (pessimistic) or positive (optimistic) way. Negative CJB is observed in depression and anxiety, conditions that burden affected individuals and caregivers. Pre-clinical animal research is key to understanding CJB and developing therapies, so a translationally relevant CJB test would be a useful addition to the existing pre-clinical rodent touchscreen test battery. We pharmacologically validated a mouse touchscreen CJB task using bupropion and tetrabenazine, agents known to induce positive and negative CJB, respectively. Additionally, we validated the task using an ecologically relevant stressor (injection and handling). Bupropion produced an optimistic-like shift in CJB whereas both tetrabenazine and saline injection 30 minutes prior to testing produced pessimistic-like shifts in CJB. These results provide a validated task to assess CJB in mice, which will allow us to ask future questions surrounding its underlying neurobiology and develop treatments for affective disorders.

Summary for Lay Audience

Affect, which refers to the emotions and feelings that we experience, influences cognitive processes such as attention, memory and decision making. During positive affective states, ambiguous cues may be more likely to be interpreted in an optimistic manner, whereas in negative affective states they may be more likely to be interpreted in a pessimistic manner. This is referred to as cognitive judgement bias (CJB). Negative CJB is observed in depression and anxiety, conditions that burden affected individuals and caregivers. It is therefore important to develop novel ways to explore the factors that affect these processes in order to develop effective treatments to target these cognitive-emotional symptoms and disorders. Additionally, the use of pre-clinical animal models in parallel with clinical populations can enable us to translate findings between mice and humans. In humans, we can use self-report measures to assess affect; however, this is not possible in animals. Therefore, researchers have used physiological and behavioural measures to infer animal affective state. Many tests previously employed to assess animal affect are aversive or use methods that may not be relevant to humans. Automated touchscreen tests for animals provide a compelling way to implement identical tests of cognition and affect in animals and humans. Thus, the main objectives of this thesis were to validate a CJB task for mice using touchscreen-based technology. To do so, we used two pharmacological agents which have previously been shown to alter affect. Bupropion, an antidepressant, and tetrabenazine, an agent which induces depressive-like symptoms were used to induce positive and negative affect, respectively. We also investigated the effects of injection and handling (mild stressor) on CJB to test for ecological validity of the task. We found that bupropion administration caused an optimistic-like shift in CJB and tetrabenazine induced a pessimistic-like shift in CJB. Additionally, an injection of saline 30 minutes prior to testing induced a pessimistic-like shift in CJB. Overall, our results suggest that our mouse CJB task can detect both positive and negative shifts in CJB. This task can be used to further understand the mechanisms underlying CJB and for testing therapeutics to treat affect-related disorders.

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