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@article{Vamvakopoulou:2022:10.3389/fpsyt.2022.998844,
author = {Vamvakopoulou, IA and Fonville, L and Hayes, A and McGonigle, J and Elliott, R and Ersche, KD and Flechais, R and Murphy, A and Orban, C and Smith, DG and Suckling, J and Taylor, EM and Deakin, B and Robbins, TW and Nutt, D and Lingford-Hughes, A and Paterson, L},
doi = {10.3389/fpsyt.2022.998844},
journal = {Frontiers in Psychiatry},
pages = {1--20},
title = {Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence},
url = {http://dx.doi.org/10.3389/fpsyt.2022.998844},
volume = {13},
year = {2022}
}

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TY  - JOUR
AB  - Introduction: Negative affective states contribute to the chronic-relapsingnature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negativeemotional processing in substance dependent individuals and healthy controls.Methodology: Functional MRI BOLD response was assessed during an evocative image task, 2h following acute administration of GSK598809 (60mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n=36) comprising alcohol-only (AO, n=19) and cocaine-alcohol polydrug (PD, n=17) groups, and matched controls (n=32) were presented with aversive and neutral images in a block design (contrast of interest: aversive>neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects.Results: No group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, andreduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups.Conclusion: Acute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology a
AU  - Vamvakopoulou,IA
AU  - Fonville,L
AU  - Hayes,A
AU  - McGonigle,J
AU  - Elliott,R
AU  - Ersche,KD
AU  - Flechais,R
AU  - Murphy,A
AU  - Orban,C
AU  - Smith,DG
AU  - Suckling,J
AU  - Taylor,EM
AU  - Deakin,B
AU  - Robbins,TW
AU  - Nutt,D
AU  - Lingford-Hughes,A
AU  - Paterson,L
DO  - 10.3389/fpsyt.2022.998844
EP  - 20
PY  - 2022///
SN  - 1664-0640
SP  - 1
TI  - Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence
T2  - Frontiers in Psychiatry
UR  - http://dx.doi.org/10.3389/fpsyt.2022.998844
UR  - https://www.frontiersin.org/articles/10.3389/fpsyt.2022.998844/full
UR  - http://hdl.handle.net/10044/1/100132
VL  - 13
ER  -

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