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Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors.

Journal article
Authors Daniel Andersson
Evelina Björnsson
Filip Bergquist
Hans Nissbrandt
Published in Experimental neurology
Volume 221
Issue 1
Pages 251-259
ISSN 1090-2430
Publication year 2010
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 251-259
Language en
Links dx.doi.org/10.1016/j.expneurol.2009...
Keywords Substantia nigra, Acetylcholine, Dopamine, Motor control, Pedunculopontine nucleus, Somatodendritic dopamine release, Muscarinic receptors
Subject categories Pharmacology and Toxicology, Physiology, Neurology

Abstract

Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.

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