Theis, Hendrik, Probst, Catharina, Fernagut, Pierre-Olivier ORCID: 0000-0002-7737-5439 and van Eimeren, Thilo ORCID: 0000-0002-6951-2325 (2021). Unlucky punches: the vulnerability-stress model for the development of impulse control disorders in Parkinson's disease. npj Parkinsons Dis., 7 (1). BERLIN: NATURE PORTFOLIO. ISSN 2373-8057

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Abstract

Impulse-control disorders are commonly observed during dopamine-replacement therapy in Parkinson's disease, but the majority of patients seems immune to this side effect. Epidemiological evidence suggests that a major risk factor may be a specific difference in the layout of the dopaminergic-reinforcement system, of which the ventral striatum is a central player. A series of imaging studies of the dopaminergic system point toward a presynaptic reduction of dopamine-reuptake transporter density and dopamine synthesis capacity. Here, we review current evidence for a vulnerability-stress model in which a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons represent a predisposing (hypodopaminergic) vulnerability. Stress (hyperdopaminergic) is delivered when dopamine replacement therapy leads to a relative overdosing of the already-sensitized ventral striatum. These alterations are consistent with consecutive changes in reinforcement mechanisms, which stimulate learning from reward and impede learning from punishment, thereby fostering the development of impulse-control disorders. This vulnerability-stress model might also provide important insights into the development of addictions in the non-Parkinsonian population.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Theis, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Probst, CatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernagut, Pierre-OlivierUNSPECIFIEDorcid.org/0000-0002-7737-5439UNSPECIFIED
van Eimeren, ThiloUNSPECIFIEDorcid.org/0000-0002-6951-2325UNSPECIFIED
URN: urn:nbn:de:hbz:38-577948
DOI: 10.1038/s41531-021-00253-z
Journal or Publication Title: npj Parkinsons Dis.
Volume: 7
Number: 1
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2373-8057
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STRIATAL DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; ORBITOFRONTAL CORTEX; WITHDRAWAL SYNDROME; TRANSPORTER GENE; SEEKING HABITS; DE-NOVO; APATHY; RECEPTOR; NEURONSMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/57794

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