Methamphetamine treatment causes delayed decrease in novelty-induced locomotor activity in mice

Neurosci Res. 2009 Oct;65(2):160-5. doi: 10.1016/j.neures.2009.06.007. Epub 2009 Jun 24.


Methamphetamine (METH) is a psychostimulant that causes damage to dopamine (DA) axons and to non-monoaminergic neurons in the brain. The aim of the present study was to investigate short- and long-term effects of neurotoxic METH treatment on novelty-induced locomotor activity in mice. Male BALB/c mice, 12-14 weeks old, were injected with saline or METH (i.p., 7.5 mg/kg x 4 times, every 2 h). Behavior and neurotoxic effects were assessed at 10 days, 3 and 5 months following drug treatment. METH administration caused marked decreases in DA levels in the mouse striatum and cortex at 10 days post-drug. However, METH did not induce any changes in novelty-induced locomotor activity. At 3 and 5 months after treatment METH-exposed mice showed significant recovery of DA levels in the striatum and cortex. In contrast, these animals demonstrated significant decreases in locomotor activity at 5 months in comparison to aged-matched control mice. Further assessment of METH toxicity using TUNEL staining showed that the drug induced increased cell death in the striatum and cortex at 3 days after administration. Taken together, these data suggest that delayed deficits in novelty-induced locomotor activity observed in METH-exposed animals are not due to neurodegeneration of DA terminals but to combined effects of METH and age-dependent dysfunction of non-DA intrinsic striatal and/or corticostriatal neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Age Factors
  • Aging / metabolism
  • Amphetamine-Related Disorders / physiopathology*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Central Nervous System Stimulants / toxicity
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Exploratory Behavior / drug effects*
  • Exploratory Behavior / physiology
  • Male
  • Methamphetamine / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / pathology


  • Central Nervous System Stimulants
  • Methamphetamine
  • Dopamine