Noradrenergic modulation of subthalamic nucleus activity: behavioral and electrophysiological evidence in intact and 6-hydroxydopamine-lesioned rats.
Journal of Neuroscience. 2007-09-05; 27(36): 9595-9606
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1. J Neurosci. 2007 Sep 5;27(36):9595-606.
Noradrenergic modulation of subthalamic nucleus activity: behavioral and
electrophysiological evidence in intact and 6-hydroxydopamine-lesioned rats.
Belujon P(1), Bezard E, Taupignon A, Bioulac B, Benazzouz A.
(1)Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5227,
Université Victor Segalen, 33076 Bordeaux Cedex, France.
The subthalamic nucleus (STN) plays a key role in the pathophysiology of
Parkinson’s disease. The modulation of the STN by norepinephrine, however, is
unknown. The present study aims at characterizing the effects of systemic
administration of noradrenergic agents on locomotor activity and on in vivo
extracellularly recorded STN neuronal activity in intact and 6-hydroxydopamine
(6-OHDA)-lesioned rats. Using selective agonists and antagonists of alpha1 and
alpha2 adrenergic receptors (ARs), we show that STN neurons have functional
alpha1- and alpha2-AR controlling STN firing with an impact on locomotor
activity. We further demonstrate that those systemic effects are supported, at
least in part, by a direct modulation of STN neuronal activity, using patch-clamp
recordings of STN neurons in brain slices. These findings support the premise
that hypokinesia is associated with an increased STN neuronal activity, and that
improvements of parkinsonian motor abnormalities are associated with a decrease
in STN activity. Our data challenge assumptions about the role of alpha1-AR and
alpha2-AR in the regulation of STN neurons in both intact and 6-OHDA-lesioned
rats and further ground the rationale for using alpha2-AR noradrenergic
antagonists in Parkinson’s disease, albeit via an unexpected mechanism.
PMID: 17804620 [Indexed for MEDLINE]