Cognition and motivation in rodent models of neuropsychiatric disorders

Abstract

Neuropsychiatric disorders are increasingly prevalent, and understanding the underlying biological, psychological, and social mechanisms which act as either risk factors or experiential symptoms of the disease is a key goal for biomedical science. A particular focus in this work is the use of animal models to probe the cognitive domains which are affected in disease models and psychopharmacological therapeutics.
In this thesis, I explore the cognitive phenotype of Dlg2, a genetic risk factor for diseases including schizophrenia, bipolar disorder, and ADHD, using heterozygous rats. Differences in cognitive flexibility are assayed on two separate protocols: a touchscreen-based visual reversal learning task and a separate visuospatial object-in-place exploration task. My work found that Dlg2^+/- rats are impaired on the extinction-phase of learning, perseverating on newly-unreinforced behaviour longer than control animals.
Separately, I study task engagement and motivation behaviour in healthy rats using a variable interval lever-pressing task, adapted to additionally assay impulsive and explorative behaviour through a regularly-changing reinforcement schedule. The effects of NMDA antagonists and scopolamine – which are of interest as both schizophrenia models and as rapid-acting antidepressants – are characterized, as is the effect of prefeeding high- and low-value food. My work replicates and expands on previous findings on the diverse effects of different NMDA antagonists, in addition to novel and divergent results with scopolamine on motivation and impulsivity compared to other pre-clinical tasks. I also discover a potential interactive effect of high- and low-value food satiety on explorative behaviour.
In summary, this work expands knowledge of the Dlg2 behavioural phenotype, as well as further characterizing the cognitive effects of a variety of clinically-relevant drugs and non-pharmacological feeding manipulations.

Date of Award	24 Jan 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Emma S J Robinson (Supervisor) & Ingeborg Hers (Supervisor)