Serotonergic neurons mediate the anxiolytic effect of L-DOPA: Neuronal correlates in the amygdala
Neurobiology of Disease. 2018-02-01; 110: 20-28
DOI: 10.1016/j.nbd.2017.11.001
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Faggiani E(1), Naudet F(1), Janssen MLF(2), Temel Y(2), Benazzouz A(3).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33076
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33076 Bordeaux, France.
(2)Department of Neuroscience and Neurosurgery, Maastricht University Medical
Center, Maastricht, The Netherlands.
(3)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33076
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33076 Bordeaux, France. Electronic address:
.
Anxiety in Parkinson’s disease is a comorbid non-motor symptom that alters the
quality of life of patients. Its neuronal substrates and those of l-Dopa
treatment are still poorly known. Using different combinations of monoaminergic
system lesions in the rat, we addressed the contribution of these systems in the
efficacy of l-DOPA on anxiety and on the neuronal activity of basolateral
amygdala (BLA), a brain structure involved in anxiety. Anxiety, locomotor
activity and motor performance were assessed using the elevated plus maze, the
open field and the skinner box, respectively. The neuronal activity of BLA was
electrophysiologically recorded and the loss of dopamine, noradrenaline and
serotonin neurons was quantified by immunohistochemistry and stereology.
Selective bilateral lesion of dopamine neurons, with or without the additional
lesions of noradrenaline and/or serotonin neurons, induced anxiety disorder.
l-Dopa significantly decreased anxiety in animals with bilateral lesion of
dopamine neurons alone or combined with that of noradrenaline neurons. In these
two groups, l-DOPA enhanced the firing rate of BLA neurons. However, in animals
with combined lesions of dopamine and serotonin neurons or in animals with
lesions of the three monoaminergic systems, l-Dopa was no longer able to
decrease anxiety behavior or to change the electrophysiological parameters of
BLA neurons. Our data provide the first evidence of the key and positive role of
the serotonergic system in the combined efficacy of l-Dopa on anxiety and the
paralleled BLA neuronal activity, suggesting that the enhancement of the
activity of serotonin neurons may boost the anxiolytic action of l-DOPA.
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