The combined depletion of monoamines alters the effectiveness of subthalamic deep brain stimulation
Neurobiology of Disease. 2015-10-01; 82: 342-348
DOI: 10.1016/j.nbd.2015.07.010
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1. Neurobiol Dis. 2015 Oct;82:342-348. doi: 10.1016/j.nbd.2015.07.010. Epub 2015
Jul 20.
The combined depletion of monoamines alters the effectiveness of subthalamic
deep brain stimulation.
Faggiani E(1), Delaville C(1), Benazzouz A(2).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33076
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
33076 Bordeaux, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33076
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
33076 Bordeaux, France. Electronic address: .
Non-motor symptoms of Parkinson’s disease are under-studied and therefore not
well treated. Here, we investigated the role of combined depletions of dopamine,
norepinephrine and/or serotonin in the manifestation of motor and non-motor
deficits in the rat. Then, we studied the impact of these depletions on the
efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS). We
performed selective depletions of dopamine, norepinephrine and serotonin, and
the behavioral effects of different combined depletions were investigated using
the open field, the elevated plus maze and the forced swim test. Bilateral
dopamine depletion alone induced locomotor deficits associated with anxiety and
mild “depressive-like” behaviors. Although additional depletions of
norepinephrine and/or serotonin did not potentiate locomotor and anxiety
disorders, combined depletions of the three monoamines dramatically exacerbated
“depressive-like” behavior. STN-DBS markedly reversed locomotor deficits and
anxiety behavior in animals with bilateral dopamine depletion alone. However,
these improvements were reduced or lost by the additional depletion of
norepinephrine and/or serotonin, indicating that the depletion of these
monoamines may interfere with the antiparkinsonian efficacy of STN-DBS.
Furthermore, our results showed that acute STN-DBS improved “depressive-like”
disorder in animals with bilateral depletion of dopamine and also in animals
with combined depletions of the three monoamines, which induced severe
immobility in the forced swim test. Our data highlight the key role of monoamine
depletions in the pathophysiology of anxiety and depressive-like disorders and
provide the first evidence of their negative consequences on the efficacy of
STN-DBS upon the motor and anxiety disorders in the context of Parkinson’s
disease.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2015.07.010
PMID: 26206409 [Indexed for MEDLINE]