Dopamine (DA) plays an essential role in the control of coordinated movements. Alterations in DA balance in the striatum lead to pathological conditions such as Parkinson's and Huntington's diseases (HD). HD is a progressive, invariably fatal neurodegenerative disease caused by a genetic mutation producing an expansion of glutamine repeats and is characterized by abnormal dance-like movements (chorea). The principal pathology is the loss of striatal and cortical projection neurons. Changes in brain DA content and receptor number contribute to abnormal movements and cognitive deficits in HD. In particular, during the early hyperkinetic stage of HD, DA levels are increased whereas expression of DA receptors is reduced. In contrast, in the late akinetic stage, DA levels are significantly decreased and resemble those of a Parkinsonian state. Time-dependent changes in DA transmission parallel biphasic changes in glutamate synaptic transmission and may enhance alterations in glutamate receptor-mediated synaptic activity. In this review, we focus on neuronal electrophysiological mechanisms that may lead to some of the motor and cognitive symptoms of HD and how they relate to dysfunction in DA neurotransmission. Based on clinical and experimental findings, we propose that some of the behavioral alterations in HD, including reduced behavioral flexibility, may be caused by altered DA modulatory function. Thus, restoring DA balance alone or in conjunction with glutamate receptor antagonists could be a viable therapeutic approach.
Keywords: Huntington's disease, behavioral inflexibility, dopamine, glutamate, electrophysiology
Citation: Chen JY, Wang EA, Cepeda C and Levine MS (2013) Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility. Front. Neurosci. 7:114. doi: 10.3389/fnins.2013.00114
Received: 08 March 2013; Accepted: 13 June 2013;
Published online: 04 July 2013.
Edited by:Giselle Petzinger, University of Southern California, USA
Reviewed by:Krishna P. Miyapuram, University of Trento, Italy
Copyright © 2013 Chen, Wang, Cepeda and Levine. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Michael S. Levine, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, School of Medicine, University of California Los Angeles, Room 58-258, 760 Westwood Plaza, Los Angeles, CA 90095, USA e-mail: firstname.lastname@example.org