Objective: To investigate the involvement of combined depletions of dopamine, norepinephrine and serotonin in the manifestation of motor and non-motor deficits and their impact on the efficacy of subthalamic deep brain stimulation (STN-DBS).

Background: Despite the focus on motor deficits, Parkinson’s disease (PD) is characterized by non-motor symptoms, including anxiety and depression. These features are under studied and therefore not well treated. While PD is classically related to the degeneration of DA cells, the involvement of norepinephrine and serotonin cell loss has been suggested. However, the precise role of combined depletion of these monoamines in the pathophysiology and therapy of PD is still not clearly determined.

Methods: Selective depletions of the three monamines were performed in the rat, and the motor and non-motor behavioral effects were quantified using several tests: the Open field for motor functions, elevated plus maze for anxiety disorder and the forced swim test for depressive-like behavior.

Results: Bilateral depletion of dopamine resulted in locomotor deficits associated with anxiety and a low level depressive-like” behavior. Although additional depletion of norepinephrine and/or serotonin did not exacerbate locomotor and anxiety disorders, combined depletions of the three monoamines dramatically potentiated “depressive-like” behavior. Interestingly, while STN-DBS dramatically reversed locomotor and anxiety disorders in animals with bilateral dopamine depletion alone, these improvements were reduced or lost by the additional depletion of norepinephrine and/or serotonin. Furthermore, our results showed that STN-DBS improved mild and also severe depressive-like” disorder in animals with bilateral dopamine depletion alone and in animals with combined depletions of the three monoamines respectively.

Conclusions: Our data highlight the key role played by combined depletion of monoamines in the pathophysiology of motor and non-motor Parkinsonian-like deficits. They provide the first evidence that the additional depletion of norepinephrine and serotonin to that of dopamine may interfere with the anti-Parkinsonian efficacy of STN-DBS on motor and anxiety disorders, but not on “depressive-like” behavior in the context of Parkinson’s disease.

A part was presented in the World Congress on Parkinson’s disease and Related Disorders 2015 Milan Italy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-the-combined-depletion-of-monoamines-on-the-effectiveness-of-deep-brain-stimulation-of-the-subthalamic-nucleus/