Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury

Neurobiol Dis. 2008 Nov;32(2):319-27. doi: 10.1016/j.nbd.2008.07.015. Epub 2008 Aug 5.


The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as a model of basal ganglia injury and Parkinson's disease. The present study investigated the effects of MPTP-induced lesioning on associative memory, conditioned fear, and affective behavior. Male C57BL/6 mice were administered saline or MPTP and separate groups were evaluated at either 7 or 30 days post-lesioning. In the social transmission of food preference test, mice showed a significant decrease in preference for familiar food 30 days post-MPTP compared to controls. Mice at both 7 and 30 days post-MPTP lesioning had increased fear extinction compared to controls. High Performance Liquid Chromatography analysis of tissues homogenates showed dopamine and serotonin were depleted in the striatum, frontal cortex, and amygdala. No changes in anxiety or depression were detected by the tail suspension, sucrose preference, light-dark preference, or hole-board tests. In conclusion, acute MPTP lesioning regimen in mice causes impairments in associative memory and conditioned fear, no mood changes, and depletion of dopamine and serotonin throughout the brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Adaptation, Physiological
  • Analysis of Variance
  • Animals
  • Basal Ganglia / injuries
  • Basal Ganglia / metabolism
  • Basal Ganglia / pathology*
  • Chromatography, High Pressure Liquid / methods
  • Conditioning, Classical / drug effects
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Exploratory Behavior
  • Fear / drug effects
  • Food Preservation / methods
  • Hindlimb Suspension
  • MPTP Poisoning* / metabolism
  • MPTP Poisoning* / pathology
  • MPTP Poisoning* / physiopathology
  • Male
  • Memory / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / pathology
  • Serotonin / metabolism*
  • Social Behavior
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism


  • Serotonin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Dopamine