Characterising the neural correlates of drug and non-drug reward in addiction: a focus on nicotine, alcohol and opiate use disorder
File(s)
Author(s)
Herlinger, Katherine
Type
Thesis
Abstract
Introduction: Nicotine, alcohol and opiate use disorders (NUD, AUD and OUD respectively) demand a great deal of health and social care resources in the UK. Understanding the underlying neurobiological mechanisms of these disorders will help us to identify novel therapeutic targets and develop pharmacotherapies and behavioural/psychological interventions to improve outcomes.
Aims: This study aimed to characterise the underlying neurobiology of NUD, AUD and OUD by using functional magnetic resonance imaging (fMRI) paradigms to probe reward processing. Two aspects of reward processing were examined: drug reward using a drug cue reactivity fMRI paradigm, and non-drug reward using a Monetary Incentive Delay task (MID) paradigm. With respect to OUD only, this study also investigated the effects Neurokinin-1 receptor (NK1) antagonism on these neural correlates.
Results: Ex-smokers displayed heightened cigarette cue reactivity compared with non-smokers (adults with obesity) in several reward processing regions including the insula and multiple regions of the prefrontal cortex (PFC). Individuals with AUD who are abstinent (AAD) did not display heightened alcohol cue reactivity compared with within recommended limits, social drinkers (ex-smokers and adults with obesity). Individuals with severe OUD maintained on methadone (MD) displayed heightened heroin cue reactivity in several regions including the frontal pole and cingulate cortex compared with controls. In MD, heightened heroin cue reactivity in these regions was reduced by the NK1 antagonist aprepitant. Ex-smokers, AAD and MD all displayed blunted striatal BOLD responses to monetary reward anticipation compared with controls. In MD this was not modulated by the NK1 antagonist aprepitant.
Conclusions: These findings indicate that disrupted drug and non-drug reward processing persists in NUD, AUD and OUD despite abstinence or substitution therapy. Aprepitant modulates drug cue reactivity in the direction indicative of clinical benefit in MD, and therefore should proceed to clinical trial.
Aims: This study aimed to characterise the underlying neurobiology of NUD, AUD and OUD by using functional magnetic resonance imaging (fMRI) paradigms to probe reward processing. Two aspects of reward processing were examined: drug reward using a drug cue reactivity fMRI paradigm, and non-drug reward using a Monetary Incentive Delay task (MID) paradigm. With respect to OUD only, this study also investigated the effects Neurokinin-1 receptor (NK1) antagonism on these neural correlates.
Results: Ex-smokers displayed heightened cigarette cue reactivity compared with non-smokers (adults with obesity) in several reward processing regions including the insula and multiple regions of the prefrontal cortex (PFC). Individuals with AUD who are abstinent (AAD) did not display heightened alcohol cue reactivity compared with within recommended limits, social drinkers (ex-smokers and adults with obesity). Individuals with severe OUD maintained on methadone (MD) displayed heightened heroin cue reactivity in several regions including the frontal pole and cingulate cortex compared with controls. In MD, heightened heroin cue reactivity in these regions was reduced by the NK1 antagonist aprepitant. Ex-smokers, AAD and MD all displayed blunted striatal BOLD responses to monetary reward anticipation compared with controls. In MD this was not modulated by the NK1 antagonist aprepitant.
Conclusions: These findings indicate that disrupted drug and non-drug reward processing persists in NUD, AUD and OUD despite abstinence or substitution therapy. Aprepitant modulates drug cue reactivity in the direction indicative of clinical benefit in MD, and therefore should proceed to clinical trial.
Version
Open Access
Date Issued
2023-10-22
Date Awarded
01/08/2024
License URL
Advisor
Lingford-Hughes, Anne
Nutt, David
Goldstone, Anthony
Sponsor
Medical Research Council (Great Britain)
Grant Number
MR/M007022/1
MR/R024197/1
Publisher Department
Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)