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Publié le December 3, 2019 | Updated on May 18, 2020

Impact of a serotonergic lesion on the expression of motor and neuropsychiatric symptoms

Mathilde MILLOT - Under the supervision of Véronique Sgambato-Faure

Parkinson’s disease (PD) is characterized by a progressive and irreversible degeneration of dopaminergic (DA) neurons localized in the substantia nigra, leading to a loss of dopamine within the target structures. When the loss of DA reaches 60 to 80 %, PD patients develop a wide range of motor (rigidity, tremor, akinesia fro example) and non-motor (depression, anxiety, apathy for example) symptoms. Dopatherapy allows the reduction of symptoms expression. But some motor and non-motor symptoms are not counteracted by those DA drugs. In addition to DA degeneration, patients present an early serotonergic (5-HT) lesion. This lesion is linked to the severity of some motor and non-motor symptoms. However, there is no causal link established between 5-HT lesion and parkinsonian symptoms. Therefore, it was essential to determine the role of 5-HT 1) in the expression of motor and non-motor symptoms 2) and in the response of DA and 5-HT treatments. For that, we used a new monkey model of PD, exhibiting a 5-HT lesion (with MDMA ‘”ecstasy”)) followed by a DA lesion (with MPTP). This model allowed us to evaluate the impact of an early 5-HT lesion on parkinsonian symptoms. We used different approaches: PET imaging, pharmacology, behavioral and neuroanatomy. The MDMA-driven early 5-HT lesion induced an anxious-like behavior on MDMA treatedmonkeys. This behavioral modification was not counteracted by 5-HT drugs (antidepressant). This MDMA lesion has also increased the severity and the progression of parkinsonian symptoms induced by DA lesion with MPTP