title: Levodopa improves motor deficits but can further disrupt cognition in a macaque Parkinson model.
abstract: BACKGROUND
  Levodopa effectively relieves motor symptoms in Parkinson's disease (PD), but has had inconsistent effects on cognition, even worsening some aspects of cognitive functioning. Therefore, remediation of PD cognitive deficits is a major unmet need. However, drug development efforts have been hampered by lack of an animal model in which motor and cognitive deficits can be examined simultaneously.
  
  
  METHODS
  Cynomolgus monkeys were trained to perform cognitive tasks and then chronically exposed to MPTP to slowly produce cognitive and motor deficits of parkinsonism.
  
  
  RESULTS
  Administration of L-dopa to these animals dose dependently improved motor functioning, but did not significantly improve cognitive performance. At doses that maximally improved motor function, additional cognitive deficits were observed. The present model of MPTP-induced parkinsonism recapitulates important motor and cognitive aspects of PD. Results with L-dopa mirror data derived from PD patients.
  
  
  CONCLUSIONS
  This model should allow more efficient testing of potential PD therapeutics to evaluate motor and cognitive functions simultaneously. © 2012 Movement Disorder Society.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jay.schneider@jefferson.edu
authors.forename: Jay S
authors.initials: JS
authors.lastname: Schneider
authors.forename: Elsa Y
authors.initials: EY
authors.lastname: Pioli
authors.forename: Yang
authors.initials: Y
authors.lastname: Jianzhong
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D007980:Levodopa / Q000627:therapeutic use*; D020267:MPTP Poisoning / Q000150:complications* / Q000188:drug therapy; D008252:Macaca fascicularis; D008297:Male; D009068:Movement / Q000187:drug effects*; D010775:Photic Stimulation; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine