Amisulpride and l-DOPA modulate subcortical brain nuclei connectivity in resting-state pharmacologic magnetic resonance imaging

  • The precise understanding of the dopaminergic (DA) system and its pharmacological modifications is crucial for diagnosis and treatment of neuropsychiatric disorders, as well as for understanding basic processes, such as motivation and reward. We probed the functional connectivity (FC) of subcortical nuclei related to the DA system according to seed regions defined according to an atlas of subcortical nuclei. We conducted a large pharmaco-fMRI study using a double-blind, placebo-controlled design, where we examined the effect of l -DOPA, a dopamine precursor, and amisulpride, a D2/D3-receptor antagonist on resting-state FC in 45 healthy young adults using a cross-over design. We examined the FC of subcortical nuclei with connection to the reward system and their reaction to opposing pharmacological probing. Amisulpride increased FC from the putamen to the precuneus and from ventral striatum to precentral gyrus. l -DOPA increased FC from the ventral tegmental area (VTA) to the insula/operculum and between ventral striatum and ventrolateral prefrontal cortex and it disrupted ventral striatal and dorsal caudate FC with the medial prefrontal cortex. In an exploratory analysis, we demonstrated that higher self-rated impulsivity goes together with a significant increase in VTA-mid-cingulate gyrus FC during l -DOPA-challenge. Therefore, our DA challenge modulated distinct large-scale subcortical connectivity networks. A dopamine-boost can increase midbrain DA nuclei connectivity to the cortex. The involvement of the VTA-cingulum connectivity in dependence of impulsivity has implications for diagnosis and therapy in disorders like ADHD.

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Author:Oliver GrimmORCiDGND, Vera Kopfer, Lea Küpper-Tetzel, Vera Deppert, Magdalena Kuhn, Moritz de GreckORCiDGND, Andreas ReifORCiDGND
Parent Title (English):Human brain mapping
Place of publication:New York, NY
Document Type:Article
Date of Publication (online):2019/12/27
Date of first Publication:2019/12/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/01/11
Tag:L-DOPA; amisulpride; dopamine; insula; pharmaco-fMRI; resting-state fMRI; ventral tegmental area
Page Number:13
First Page:1806
Last Page:1818
Financial support for this study was received from the European Union's Horizon 2020 research and innovation program under grant agreement 667302: Comorbid Conditions of ADHD (CoCA). Prof. Dr. Andreas Reif received personal fees from MEDICE Arzneimittel Pütter GmbH & Co. KG, Shire PLC, neuraxpharm Arzneimittel GmbH, Janssen-Cilag GmbH and Servier Deutschland GmbH present or dur- ing 36 months prior to publication. Oliver Grimm received personal fees from MEDICE Arzneimittel Pütter GmbH & Co. KG.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0