The effects of serotonergic manipulation on behavioural and neural correlates of reward processing

Thesis

The serotonin system is implicated in a wide variety of mental illnesses; indeed, its modulation is utilised in treatments for such illnesses. However, such serotonergic-based treatments are not effective for all individuals, or perhaps more specifically for all symptoms an individual experiences. One such symptom is anhedonia, commonly defined as the loss of pleasure. Anhedonia is often studied through reward processing, that is a series of stages that include the experience of a reward (liking), motivation to acquire it (wanting) and learning about how to obtain the reward again (learning).

Contrasting evidence exists on the influence of serotonergic modulation on these stages, with some indicating the commonly used selective serotonin reuptake inhibitors (SSRI) may worsen reward processing, which would be of high clinical relevance.

The central serotonin system is anatomically widespread and diverse in its downstream effects. One key component of the system is the 5-HT1A receptor, whilst well characterised behaviourally in animals, there is a paucity of evidence in humans. The scarcity of evidence extends to not only anhedonia but also cognition and emotional processing. It is important to clarify as any serotonergic modulation will almost certainly be influenced by the response of the 5-HT1A receptor.

The goal of this thesis is to explore the effect of serotonergic interventions on the separate stages of reward processing both at behavioural and neural level in healthy volunteers using a randomised, double-blind, placebo-controlled, between-subjects design. It also investigates the effects of the 5-HT1A receptor agonist buspirone on cognition and emotional processing.

This thesis demonstrates the divergent role of different serotonergic interventions, used over different durations, on reward processing. This is of relevance to the transdiagnostic symptom of anhedonia. It may enable further work to identify what, and how, specific components of the serotonergic system can influence anhedonia in clinical populations and treatments therein.

Authors: Smith, ALW

• DOI: 10.5287/ora-kemadxp98
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: serotonin; motivation; reward; anhedonia
• Subjects: Serotonin uptake inhibitors; Reward (Psychology); Magnetic resonance imaging; Serotonin--Agonists; Motivation (Psychology)