title: Selective loss of dopaminergic neurons in the substantia nigra pars compacta after systemic administration of MPTP facilitates extinction learning.
abstract: OBJECTIVE
  Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). In PD, thinking and retrieval deficits often arise from cognitive impairments. However, the mechanism of cognitive disorders in PD remains unknown. Therefore, we investigated cognitive function in PD model mice produced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which specifically destroys the DAergic neurons in the SNpc.
  
  
  METHODS
  We evaluated the cognitive function of MPTP-treated mice (PD mice) using the contextual fear conditioning test. In the test, each experiment consists of three phases: training, re-exposure, and testing. Mice were trained with a foot shock (a weak unconditioned stimulus: 1mA/2s duration, once, or an intense unconditioned stimulus: 2mA/2s duration, twice), and 24h later, mice were re-exposed to the training context for 3min to determine reconsolidation or 30min to determine extinction. The percentage of time spent freezing was measured during the test session as indexes of memory consolidation, reconsolidation, and extinction.
  
  
  RESULTS
  Reconsolidation of PD mice occurred normally but memory extinction was facilitated in PD mice compared to control mice. Moreover, memory retention in PD mice was attenuated earlier than in controls following repeated conditioned stimuli every day.
  
  
  CONCLUSIONS
  PD mice with selective loss of DAergic neurons in the SNpc showed attenuated memory retention, probably via facilitated extinction learning.
authors.affiliation: Department of Pathogenetic Veterinary Science, The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Pathogenetic Veterinary Science, The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Yoshikage
authors.initials: Y
authors.lastname: Muroi
authors.affiliation: Department of Pathogenetic Veterinary Science, The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; The Laboratory of Pharmacology, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Unno
authors.affiliation: Department of Pathogenetic Veterinary Science, The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan. Electronic address: ishii@obihiro.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishii
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology; D003214:Conditioning, Classical / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology*; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D065842:Pars Compacta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011699:Putamen / Q000187:drug effects / Q000473:pathology; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
keywords: Dopamine; Extinction; MPTP; Parkinson's disease; Reconsolidation