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Further characterisation of psychosis-like behaviours induced by L-DOPA in the MPTP-lesioned marmoset

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Abstract

Parkinson’s disease (PD) psychosis afflicts over half of patients and poses a significant burden on quality of life. The aetiology of PD psychosis is multifactorial and likely arises from the complex interaction between dopamine replacement therapy and disease state. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset is a validated model to predict the efficacy of therapeutic compounds for treatment-related complications, including PD psychosis. In this model, psychosis-like behaviours (PLBs) encompass stereotypies that are idiosyncratic in nature and reproducible with each L-3,4-dihydroxyphenylanaline (L-DOPA) administration. In the present study, we sought to expand upon the existing repertoire of PLBs through the characterisation of novel stereotypical behaviours that appear dependent on the environment. We then discuss our findings in the context of clinical reports on stereotypical behaviours termed “punding” in subjects with PD, which consists of stereotypical repetitive and senseless behaviours. The poor understanding of the pathophysiology governing punding and consequent lack of effective therapies stand to benefit from enhanced characterisation of these stereotypical behaviours in a validated pre-clinical model. We hope that further characterisation of PLBs in the MPTP-lesioned marmoset will be helpful in the evaluation of interventions that seek to alleviate PD psychosis symptoms.

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Funding

CK has scholarships from Parkinson Canada and Fonds de Recherche Québec – Santé. PH has research support from Parkinson Canada, Parkinson Québec, Fonds de Recherche Québec – Santé, the Weston Brain Institute, the Michael J Fox Foundation for Parkinson’s Research, the Natural Sciences and Engineering Research Council of Canada and Healthy Brains for Healthy Lives.

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Authors and Affiliations

  1. Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), 3801 University St, Montreal, QC, H3A 2B4, Canada

    Cynthia Kwan & Philippe Huot

  2. Comparative Medicine & Animal Resource Centre, McGill University, Montreal, QC, Canada

    Stephen G. Nuara & Jim C. Gourdon

  3. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

    Philippe Huot

  4. Movement Disorder Clinic, Division of Neurology, Department of Neuroscience, McGill University Health Centre, Montreal, QC, Canada

    Philippe Huot

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  1. Cynthia Kwan
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  2. Stephen G. Nuara
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  4. Philippe Huot
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Contributions

CK and PH conceived and designed research. CK, SGN and PH conducted experiments. CK analysed data. CK wrote the manuscript. SGN, JCG and PH revised the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Philippe Huot.

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Experiments were approved by McGill University and the Montreal Neurological Institute-Hospital (The Neuro) Animal Care Committees, which are in accordance with the regulations defined by the Canadian Council on Animal Care.

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Kwan, C., Nuara, S.G., Gourdon, J.C. et al. Further characterisation of psychosis-like behaviours induced by L-DOPA in the MPTP-lesioned marmoset. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1685–1692 (2021). https://doi.org/10.1007/s00210-021-02090-6

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