Behavioural analysis of cognitive, motivational, and hedonic aspects of reward processing

Lewis, Lucy ORCID: https://orcid.org/0000-0002-8656-9112 2021. Behavioural analysis of cognitive, motivational, and hedonic aspects of reward processing. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Processing of rewards involves three major mechanisms of cognition, motivation, and hedonic response, and reward-related deficits seen in psychiatric disorders encompass disruptions in these aspects of reward processing. Heterogeneity and poor treatment efficacy in psychiatric patients highlight the need to elucidate the neurobiological mechanisms underpinning these deficits as isolated mechanisms, rather than as a single entity. To understand the neurobiology of individual aspects of reward processing, preclinical rodent assays need to be capable of dissociating these. Thus, this thesis evaluated three assays aiming to measure cognitive, hedonic, or motivational deficits separately. Here, I also investigated the neurobiological mechanisms underpinning these aspects through the application of these assays to preclinical models of psychiatric disease. The flavour modified affective bias test (m-ABT) was evaluated as an automated version of an established assay for cognitive bias deficits, but despite showing initial promise in being capable of measuring positive biases induced by reward value (Chapter 2), this assay did not reliably measure deficits in preclinical models of psychiatric disease (Chapter 3). However, the use of this assay in the transgenic CACNA1C heterozygous knockout rat model highlighted some possible cognitive bias deficits that warrant further investigation in alternative assays. In contrast, lick cluster analysis (LCA) was used to measure hedonic response to rewards (Chapter 4) and was able to demonstrate a lack of hedonic deficit in the chronic IFN-α model, as well as the rat chronic corticosterone (CORT) model which showed a deficit in other literature using alternative, less-specific methods, indicating this LCA assay could be used to dissociate hedonic response from other aspects of reward processing more reliably. Furthermore, the effort-related choice paradigm (EfR) was applied to acute and chronic IFN-α and CORT models, as well as the transgenic CACNA1C heterozygous knockout rat model (Chapter 5). Acute treatment with IFN-α and CORT did not impair motivation for reward, whereas chronic treatment indicated a potential deficit that was not clearly demonstrated possibly due to experimental errors. The CACNA1C model showed no deficit in motivation for reward, but potential influence on habitual responding or impulse control, thus indicating the EfR assay could be used to dissociate motivational deficits from other aspects of reward processing as well as influences from other mechanisms. Neurobiological characterisation of the chronic CORT and IFN-α models (Chapter 6) found no clear impact of CORT on neurogenesis or glutamatergic neurotransmission, but IFN-α resulted in elevated neurogenic markers and NR2B expression in the hippocampus.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology
Funders:	BBSRC SWBio
Date of First Compliant Deposit:	30 November 2021
Date of Acceptance:	30 November 2021
Last Modified:	10 Nov 2022 10:09
URI:	https://orca.cardiff.ac.uk/id/eprint/145829

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