title: Dopamine receptor 3 might be an essential molecule in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.
abstract: BACKGROUND
  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson's disease (PD)-like neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) via its oxidized product, 1-methyl-4-phenylpyridinium (MPP+), which is transported by the dopamine (DA) transporter into DA nerve terminals. DA receptor subtype 3 (D3 receptor) participates in neurotransmitter transport, gene regulation in the DA system, physiological accommodation via G protein-coupled superfamily receptors and other physiological processes in the nervous system. This study investigated the possible correlation between D3 receptors and MPTP-induced neurotoxicity. A series of behavioral experiments and histological analyses were conducted in D3 receptor-deficient mice, using an MPTP-induced model of PD.
  
  
  RESULTS
  After the fourth MPTP injection, wild-type animals that received 15 mg/kg per day displayed significant neurotoxin-related bradykinesia. D3 receptor-deficient mice displayed attenuated MPTP-induced locomotor activity changes. Consistent with the behavioral observations, further neurohistological assessment showed that MPTP-induced neuronal damage in the SNpc was reduced in D3 receptor-deficient mice.
  
  
  CONCLUSIONS
  Our study indicates that the D3 receptor might be an essential molecule in MPTP-induced PD and provides a new molecular mechanism for MPTP neurotoxicity.
authors.affiliation: Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying-yin
authors.initials: YY
authors.lastname: Ni
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jia-wei
authors.initials: JW
authors.lastname: Lu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Wu
authors.forename: Ming-min
authors.initials: MM
authors.lastname: Gu
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Lu
authors.forename: Zhu-gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Ren
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011597:Psychomotor Performance / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050637:Receptors, Dopamine D3; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
references.citation: J Neurochem. 2003 Jul;86(2):290-7
references.pmid: 12871570
references.citation: Neuroreport. 2000 Aug 3;11(11):2395-9
references.pmid: 10943692
references.citation: Pharmacol Rev. 1980 Sep;32(3):229-313
references.pmid: 6117090
references.citation: J Neurochem. 1997 Sep;69(3):1322-5
references.pmid: 9282960
references.citation: Ann N Y Acad Sci. 1992 May 11;648:96-104
references.pmid: 1637076
references.citation: Neurochem Res. 2009 Feb;34(2):327-32
references.pmid: 18612813
references.citation: Nat Clin Pract Neurol. 2006 Jul;2(7):382-92
references.pmid: 16932589
references.citation: Res Commun Chem Pathol Pharmacol. 1985 Dec;50(3):435-41
references.pmid: 3878557
references.citation: Neurosci Lett. 2010 Nov 26;485(3):256-60
references.pmid: 20849922
references.citation: Int J Med Chem. 2011;2011:403039
references.pmid: 25954517
references.citation: Physiol Rev. 1998 Jan;78(1):189-225
references.pmid: 9457173
references.citation: Nat Rev Neurol. 2009 Oct;5(10):533-41
references.pmid: 19724249
references.citation: Neuron. 1997 Oct;19(4):837-48
references.pmid: 9354330
references.citation: Nature. 1979 Jan 11;277(5692):93-6
references.pmid: 215920
references.citation: Exp Neurobiol. 2011 Mar;20(1):1-17
references.pmid: 22110357
references.citation: Nat Protoc. 2007;2(1):141-51
references.pmid: 17401348
references.citation: EMBO J. 2012 Jun 26;31(14):3038-62
references.pmid: 22735187
references.citation: Acta Neurobiol Exp (Wars). 2011;71(2):269-80
references.pmid: 21731080
references.citation: J Biol Chem. 2000 Dec 8;275(49):38944-8
references.pmid: 11007776
references.citation: J Neurosci. 2002 Jul 1;22(13):5619-29
references.pmid: 12097513
references.citation: Nat Clin Pract Neurol. 2006 Mar;2(3):136-46
references.pmid: 16932540
references.citation: N Engl J Med. 2012 Oct 18;367(16):1529-38
references.pmid: 23075179
references.citation: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1945-9
references.pmid: 8700864
references.citation: Science. 2001 Nov 2;294(5544):1021-4
references.pmid: 11691978