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Subthalamic nucleus stimulation impairs motivation: Implication for apathy in Parkinson's disease.

on the February 6, 2020
Background: Apathy is one of the most disabling neuropsychiatric symptoms in Parkinson’s disease (PD) patients, and has a higher prevalence in patients under subthalamic nucleus deep brain stimulation (STN-DBS). Indeed, despite its effectiveness for alleviating PD motor symptoms, its neuropsychiatric repercussion has not been fully uncovered yet. Because it can be alleviated by dopaminergic therapies, especially D2 and D3 dopaminergic receptor (D2R/D3R) agonists, the commonest explanation proposed for apathy after STN-DBS is a too strong reduction of dopaminergic treatments.

Objectives: Whether or not STN-DBS can induce apathetic behaviors remains an important matter of concern. We aimed at unambiguously addressing this question of the motivational effects of chronic STN-DBS.

Methods: We longitudinally assessed the motivational effects of chronic STN-DBS, by using innovative wireless micro-stimulators allowing continuous stimulation of STN in freely moving rats, and a pharmacological therapeutic approach.

Results: We showed for the first time that STN-DBS induces a motivational deficit in naïve rats and intensifies those existing in a rodent model of PD neuropsychiatric symptoms. As reported from clinical studies, this loss of motivation was fully reversed by chronic treatment with pramipexole, a D2R/D3R agonist.
Conclusion: Taken together, these data provide experimental evidence that chronic STN-DBS by itself can induce a loss of motivation, reminiscent of apathy, independently of the dopaminergic neurodegenerative process or reduction of dopamine replacement therapy, presumably reflecting a dopaminergic driven deficit. Therefore, our data help to clarify and reconcile conflicting clinical observations by highlighting some of the mechanisms of the neuropsychiatric side-effects induced by chronic STN-DBS.


Legend : Deep brain stimulation of the subthalamic nucleus (STN-DBS) induces a motivational deficit fully reversed by the pramipexole (PPX) in normal rat. Time course of the =reward obtained by normal rats, stimulated or not, during a 14-days sucrose self-administration test. Control + Veh: n = 22; Control + PPX: n = 22; STN-DBS + Veh: n = 13; STN-DBS + PPX: n = 8. Data shown as means +/- SEM. Control + Veh versus STN-DBS + Veh: *p < .05; **p < .01; STN-DBS + Veh versus STN-DBS + PPX: #p < .05.

References : 
Subthalamic nucleus stimulation impairs motivation: Implication for apathy in Parkinson's disease.
Vachez Y, Carcenac C, Magnard R, Kerkerian-Le Goff L, Salin P, Savasta M, Carnicella S, Boulet S.
Mov Disord. 2020 Jan 13.
doi: 10.1002/mds.27953. PMID: 31930749


Updated on February 6, 2020

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