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The Journal of Neuroscience, September 17, 2008, 28(38):9575-9584; doi:10.1523/JNEUROSCI.3465-08.2008

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Neurobiology of Disease
Behavioral Recovery in MPTP-Treated Monkeys: Neurochemical Mechanisms Studied by Intrastriatal Microdialysis

Sabrina Boulet,^1,2,3 Stéphanie Mounayar,^4,5 Annie Poupard,^1,2,3 Anne Bertrand,^1,2,3 Caroline Jan,^4,5 Mathias Pessiglione,^4,5 Etienne C. Hirsch,^4,5 Claude Feuerstein,^1,2,3 Chantal François,^4,5 Jean Féger,^4,5 Marc Savasta,^1,2,3 * and Léon Tremblay^6 *

¹Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique des Réseaux Neuronaux du Mouvement and ²Centre Hospitalier Universitaire de Grenoble, Grenoble F-38043 Cedex 09, France, ³Université Joseph Fourier, Grenoble F-38041 Cedex 09, France, ⁴Institut National de la Santé et de la Recherche Médicale, Unité 679 and ⁵Université Pierre et Marie Curie-Paris 6, Institut Fédératif de Recherche de Neurosciences Unité Mixte de Recherche (UMR) S679, Paris F-75013, France, and ⁶Institut des Neurosciences Cognitives–UMR 5229, Centre National de la Recherche Scientifique–Université de Lyon 1, Bron F-69675 Cedex, France

Correspondence should be addressed to Marc Savasta, Grenoble Institut des Neurosciences, Institut National de la Santé et de la Recherche Médicale U836, Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043 Cedex 09, France. Email: Marc.Savasta{at}ujf-grenoble.fr

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 specific 1-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.

Key words: Parkinson's disease; recovery; MPTP; primate; microdialysis; serotonin

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Received July 23, 2008; accepted Aug. 15, 2008.

Correspondence should be addressed to Marc Savasta, Grenoble Institut des Neurosciences, Institut National de la Santé et de la Recherche Médicale U836, Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043 Cedex 09, France. Email: Marc.Savasta{at}ujf-grenoble.fr

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