1. Behavioral Recovery in MPTP-Treated Monkeys: Neurochemical Mechanisms Studied by Intrastriatal Microdialysis
- Author
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Mathias Pessiglione, Annie Poupard, Claude Feuerstein, Caroline Jan, Marc Savasta, Etienne C. Hirsch, Chantal François, Jean Féger, Sabrina Boulet, Léon Tremblay, Stéphanie Mounayar, Anne Bertrand, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Collaboration, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and Savasta, Marc
- Subjects
Male ,Parkinson's disease ,Dopamine ,Microdialysis ,MESH: Movement ,MESH: gamma-Aminobutyric Acid ,Striatum ,MESH: Neurotransmitter Agents ,MESH: Down-Regulation ,MESH: Corpus Striatum ,chemistry.chemical_compound ,0302 clinical medicine ,Chlorocebus aethiops ,MESH: Behavior, Animal ,MESH: Up-Regulation ,MESH: Homovanillic Acid ,MESH: Animals ,MESH: Microdialysis ,gamma-Aminobutyric Acid ,Neurotransmitter Agents ,0303 health sciences ,Behavior, Animal ,General Neuroscience ,MPTP ,Homovanillic acid ,Glutamate receptor ,Articles ,MESH: Glutamic Acid ,Hydroxyindoleacetic Acid ,MESH: Recovery of Function ,MESH: 3,4-Dihydroxyphenylacetic Acid ,Up-Regulation ,3. Good health ,Psychology ,Serotonin ,medicine.medical_specialty ,Movement ,Down-Regulation ,Glutamic Acid ,MESH: Dopamine ,MESH: Hydroxyindoleacetic Acid ,03 medical and health sciences ,Neurochemical ,Parkinsonian Disorders ,Internal medicine ,medicine ,Animals ,030304 developmental biology ,MESH: Parkinsonian Disorders ,Extracellular Fluid ,Homovanillic Acid ,Recovery of Function ,medicine.disease ,MESH: Cercopithecus aethiops ,Corpus Striatum ,MESH: Male ,Disease Models, Animal ,Endocrinology ,MESH: Extracellular Fluid ,nervous system ,chemistry ,3,4-Dihydroxyphenylacetic Acid ,MESH: Serotonin ,MESH: Disease Models, Animal ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Parkinson's disease (PD) patients express motor symptoms only after 60–80% striatal dopamine (DA) depletion. The presymptomatic phase of the disease may be sustained by biochemical modifications within the striatum. We used an appropriate specific1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model (Mounayar et al., 2007) to study the compensatory mechanisms operating in recovery from PD motor symptoms. We assessed the levels of DA and its metabolites (DOPAC, homovanillic acid), GABA, glutamate (Glu), serotonin (5-HT) and its metabolite (5HIAA) by repeated intracerebral microdialysis in awake animals before exposure to MPTP during full expression of the motor symptoms induced by MPTP and after recovery from these symptoms. Measurements were obtained from two functionally and anatomically different striatal areas: the associative-limbic territory and sensorimotor territory. Animals with motor symptoms displayed an extremely large decrease in levels of DA and its metabolites and an increase in Glu and GABA levels, as reported by other studies. However, we show here for the first time that serotonin levels increased in these animals. We found that increases in DA levels in the sensorimotor and/or associative-limbic territory and high levels of 5-HT and of its metabolite, 5HIAA, were associated with recovery from motor symptoms in this model. Determining whether similar changes in DA and 5-HT levels are involved in the compensatory mechanisms delaying the appearance of motor symptoms in the early stages of PD might make it possible to develop new treatment strategies for the disease.
- Published
- 2008