%0 Journal Article
%T Imbalanced Dopaminergic Transmission Mediated by Serotonergic Neurons in L-DOPA-Induced Dyskinesia
%A Sylvia Navailles
%A Philippe De Deurwaerd¨¨re
%J Parkinson's Disease
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/323686
%X L-DOPA-induced dyskinesias (LIDs) are one of the main motor side effects of L-DOPA therapy in Parkinson's disease. The review will consider the biochemical evidence indicating that the serotonergic neurons are involved in the dopaminergic effects of L-DOPA in the brain. The consequences are an ectopic and aberrant release of dopamine that follows the serotonergic innervation of the brain. After mid- to long-term treatment with L-DOPA, the pattern of L-DOPA-induced dopamine release is modified. In several brain regions, its effect is dramatically reduced while, in the striatum, its effect is quite preserved. LIDs could appear when the dopaminergic effects of L-DOPA fall in brain areas such as the cortex, enhancing the subcortical impact of dopamine and promoting aberrant motor responses. The consideration of the serotonergic system in the core mechanism of action of L-DOPA opens an important reserve of possible strategies to limit LIDs. 1. Introduction Parkinson¡¯s disease is the second most devastating neurodegenerative disease affecting more than 6 million people worldwide and whose prevalence is expected to double within the next twenty years [1]. This neurological disorder is characterized by the progressive loss of mesencephalic dopaminergic (DA) neurons from the substantia nigra pars compacta and associated with numerous motor symptoms (bradykinesia, rigidity, and tremor) [2, 3]. L-DOPA, the precursor of DA, has been introduced in the mid 60¡¯s as a miracle pill to prevent the motor symptoms [4, 5]. However, upon chronic use of this medication, its efficacy slowly decreases leading to increase the doses of L-DOPA, which generate numerous side effects. After 5 to 10 years of L-DOPA treatment, Parkinsonian patients develop dyskinesias [6], which consist of stereotypical choreic or ballistic movements involving mostly the head, trunk, and limbs [7]. These abnormal involuntary movements are often more debilitating than the motor symptoms themselves. Preclinical research has permitted validating animal models to study the mechanisms of L-DOPA-induced dyskinesias (LIDs). The most commonly used rat model that shows best face and predictive validity, has been developed by Cenci and collaborators [8, 9] by producing severe lesion of the nigrostriatal DA pathway in adult rats with the unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle [10, 11]. A chronic treatment with L-DOPA for 3 weeks at low therapeutic doses (6¨C10£¿mg/kg) induced axial, limb, and orolingual abnormal involuntary movements (ALO AIMs) of variable occurrence and
%U http://www.hindawi.com/journals/pd/2012/323686/