Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment

Abstract Dopamine replacement therapy for Parkinson’s disease can induce impulsive-compulsive behaviours (ICBs). Here we compare the D2/3 agonist ropinirole and L-DOPA, given alone or combined, with regard to their potential to induce ICBs in rats sustaining bilateral striatal injections of 6-hydrox...

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Main Authors: Mirjam Wolfschlag, Elena Espa, Katrine Skovgård, Pär Halje, Maria Angela Cenci
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-00996-z
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author Mirjam Wolfschlag
Elena Espa
Katrine Skovgård
Pär Halje
Maria Angela Cenci
author_facet Mirjam Wolfschlag
Elena Espa
Katrine Skovgård
Pär Halje
Maria Angela Cenci
author_sort Mirjam Wolfschlag
collection DOAJ
description Abstract Dopamine replacement therapy for Parkinson’s disease can induce impulsive-compulsive behaviours (ICBs). Here we compare the D2/3 agonist ropinirole and L-DOPA, given alone or combined, with regard to their potential to induce ICBs in rats sustaining bilateral striatal injections of 6-hydroxydopamine. Daily treatment with ropinirole (2.5 mg/kg), L-DOPA (24.0 mg/kg), or their combination was given for six weeks while animals were examined using tests of compulsive checking and motor stereotypies not previously used in the ICB literature. Independently of L-DOPA cotreatment, ropinirole induced a stereotyped hyperactivity pattern, compulsive checking, and maladaptive choices in the rat version of the Iowa gambling task. Compared to both L-DOPA and vehicle, ropinirole elicited a distinct pattern of striatal neuroactivity, shifting the expression of a cellular activity marker from dorsolateral to centro-medial regions. Our results reveal quite distinct profiles of ICBs and striatal activation upon treatment with ropinirole or L-DOPA, providing clues of therapeutic relevance to Parkinson’s ICBs.
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issn 2373-8057
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publishDate 2025-05-01
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series npj Parkinson's Disease
spelling doaj-art-79539613dfdc4f17bfebe3fd73d450fa2025-08-20T04:01:26ZengNature Portfolionpj Parkinson's Disease2373-80572025-05-0111111810.1038/s41531-025-00996-zImpulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatmentMirjam Wolfschlag0Elena Espa1Katrine Skovgård2Pär Halje3Maria Angela Cenci4Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund UniversityBasal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund UniversityBasal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund UniversityThe Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund UniversityBasal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund UniversityAbstract Dopamine replacement therapy for Parkinson’s disease can induce impulsive-compulsive behaviours (ICBs). Here we compare the D2/3 agonist ropinirole and L-DOPA, given alone or combined, with regard to their potential to induce ICBs in rats sustaining bilateral striatal injections of 6-hydroxydopamine. Daily treatment with ropinirole (2.5 mg/kg), L-DOPA (24.0 mg/kg), or their combination was given for six weeks while animals were examined using tests of compulsive checking and motor stereotypies not previously used in the ICB literature. Independently of L-DOPA cotreatment, ropinirole induced a stereotyped hyperactivity pattern, compulsive checking, and maladaptive choices in the rat version of the Iowa gambling task. Compared to both L-DOPA and vehicle, ropinirole elicited a distinct pattern of striatal neuroactivity, shifting the expression of a cellular activity marker from dorsolateral to centro-medial regions. Our results reveal quite distinct profiles of ICBs and striatal activation upon treatment with ropinirole or L-DOPA, providing clues of therapeutic relevance to Parkinson’s ICBs.https://doi.org/10.1038/s41531-025-00996-z
spellingShingle Mirjam Wolfschlag
Elena Espa
Katrine Skovgård
Pär Halje
Maria Angela Cenci
Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment
npj Parkinson's Disease
title Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment
title_full Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment
title_fullStr Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment
title_full_unstemmed Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment
title_short Impulsive-compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under D2/3 agonist and L-DOPA treatment
title_sort impulsive compulsive behaviours and striatal neuroactivity in mildly parkinsonian rats under d2 3 agonist and l dopa treatment
url https://doi.org/10.1038/s41531-025-00996-z
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