title: Behavioral recovery in MPTP-treated monkeys: neurochemical mechanisms studied by intrastriatal microdialysis.
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 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043 Cedex 09, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Boulet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mounayar
authors.forename: Annie
authors.initials: A
authors.lastname: Poupard
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.forename: Caroline
authors.initials: C
authors.lastname: Jan
authors.forename: Mathias
authors.initials: M
authors.lastname: Pessiglione
authors.forename: Etienne C
authors.initials: EC
authors.lastname: Hirsch
authors.forename: Claude
authors.initials: C
authors.lastname: Feuerstein
authors.forename: Chantal
authors.initials: C
authors.lastname: François
authors.forename: Jean
authors.initials: J
authors.lastname: Féger
authors.forename: Marc
authors.initials: M
authors.lastname: Savasta
authors.forename: Léon
authors.initials: L
authors.lastname: Tremblay
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002522:Chlorocebus aethiops; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009068:Movement / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D006719:Homovanillic Acid
references.citation: Neurosci Lett. 1990 Jul 31;115(2-3):248-52
references.pmid: 1978265
references.citation: Neuroscience. 1989;33(2):323-31
references.pmid: 2622529
references.citation: Brain Res. 1990 Nov 26;534(1-2):25-36
references.pmid: 2073585
references.citation: Adv Drug Deliv Rev. 2000 Dec 15;45(2-3):125-48
references.pmid: 11108971
references.citation: Brain Res. 1996 Feb 19;709(2):319-25
references.pmid: 8833770
references.citation: J Neurosci. 2001 Sep 1;21(17):6853-61
references.pmid: 11517273
references.citation: Methods. 2001 Jan;23(1):3-9
references.pmid: 11162145
references.citation: Life Sci. 1986 Aug 25;39(8):699-74
references.pmid: 2874471
references.citation: J Comp Neurol. 1999 Nov 22;414(3):334-47
references.pmid: 10516600
references.citation: Eur J Neurosci. 2008 Apr;27(7):1647-58
references.pmid: 18380666
references.citation: J Chem Neuroanat. 2001 Jul;22(1-2):3-12
references.pmid: 11470551
references.citation: Exp Neurol. 1990 Nov;110(2):187-93
references.pmid: 1699780
references.citation: J Neurosci Res. 2006 Feb 1;83(2):332-47
references.pmid: 16385585
references.citation: Exp Neurol. 2003 Mar;180(1):74-87
references.pmid: 12668150
references.citation: Eur J Pharmacol. 1991 Jul 23;200(1):1-8
references.pmid: 1769366
references.citation: Brain. 2007 Nov;130(Pt 11):2898-914
references.pmid: 17855373
references.citation: Adv Neurol. 1987;45:75-7
references.pmid: 3825737
references.citation: Natl Inst Drug Abuse Res Monogr Ser. 1975 Nov;(3):13-21
references.pmid: 787796
references.citation: Brain Res. 1988 May 31;450(1-2):209-24
references.pmid: 3135914
references.citation: N Engl J Med. 1988 Apr 7;318(14):876-80
references.pmid: 3352672
references.citation: Eur J Neurosci. 2000 Aug;12(8):2892-900
references.pmid: 10971632
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1998 Feb;22(2):311-7
references.pmid: 9608603
references.citation: J Neurosci Methods. 1994 Nov;55(1):1-6
references.pmid: 7891457
references.citation: Mov Disord. 2003 Mar;18(3):241-53
references.pmid: 12621627
references.citation: Brain Res. 1980 Aug 11;195(1):123-37
references.pmid: 6105003
references.citation: J Neurochem. 1997 Feb;68(2):659-66
references.pmid: 9003053
references.citation: Brain Res Bull. 1993;31(5):463-70
references.pmid: 8098651
references.citation: Brain Res. 2001 Mar 2;893(1-2):178-85
references.pmid: 11223005
references.citation: Crit Rev Neurobiol. 2000;14(2):143-63
references.pmid: 11513243
references.citation: Brain Res. 1990 Jun 11;519(1-2):122-8
references.pmid: 2397401
references.citation: Brain Res. 1994 Apr 18;643(1-2):86-91
references.pmid: 8032935
references.citation: Exp Brain Res. 1993;96(1):100-6
references.pmid: 7902292
references.citation: Brain Res. 1987 Jul 14;415(2):293-9
references.pmid: 3496938
references.citation: Prog Neurobiol. 1996 Jun;49(3):215-66
references.pmid: 8878304
references.citation: Neuroscience. 1991;44(2):421-9
references.pmid: 1944893
references.citation: Brain Res. 1991 Aug 9;556(1):108-16
references.pmid: 1718555
references.citation: Neuroscience. 1991;44(3):591-605
references.pmid: 1754053
references.citation: Eur J Neurosci. 2000 Dec;12(12):4525-35
references.pmid: 11122363
references.citation: Neuroscience. 1997 Nov;81(2):399-404
references.pmid: 9300430
references.citation: Exp Neurol. 1990 Nov;110(2):181-6
references.pmid: 2226698
references.citation: Eur J Neurosci. 2003 Oct;18(7):2082-6
references.pmid: 14622241
references.citation: Dev Neurosci. 2001;23(1):78-83
references.pmid: 11173929
references.citation: Acta Physiol Scand. 1986 Sep;128(1):9-14
references.pmid: 2876587
references.citation: J Neurochem. 2006 Feb;96(4):960-72
references.pmid: 16412097
references.citation: J Neuropathol Exp Neurol. 2003 Dec;62(12):1228-40
references.pmid: 14692699
references.citation: Brain Res. 1991 Dec 13;567(1):127-32
references.pmid: 1815820
references.citation: Neuroscience. 2000;95(2):399-408
references.pmid: 10658619
references.citation: Neurosci Lett. 1989 Jul 3;101(3):305-10
references.pmid: 2505199
references.citation: Neurobiol Dis. 1997;4(3-4):247-53
references.pmid: 9361301
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1993 Nov;17(6):887-903
references.pmid: 8278600
references.citation: Brain Res. 1983 Sep 26;275(2):321-8
references.pmid: 6626985
references.citation: Trends Neurosci. 1990 Jul;13(7):290-6
references.pmid: 1695406
references.citation: Neuroscience. 1999 Jan;88(1):1-16
references.pmid: 10051185
references.citation: Neurology. 1998 Aug;51(2 Suppl 2):S2-9
references.pmid: 9711973
references.citation: J Neurol Sci. 1973 Dec;20(4):415-55
references.pmid: 4272516
references.citation: J Neurosci. 2000 Jul 1;20(13):5102-14
references.pmid: 10864967
references.citation: J Pharmacol Exp Ther. 1994 Sep;270(3):1158-65
references.pmid: 7932166
references.citation: Trends Neurosci. 2003 Aug;26(8):436-43
references.pmid: 12900175