npj Parkinson's Disease (May 2025)

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

  • Mirjam Wolfschlag,
  • Elena Espa,
  • Katrine Skovgård,
  • Pär Halje,
  • Maria Angela Cenci

DOI
https://doi.org/10.1038/s41531-025-00996-z
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 18

Abstract

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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.