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

Irina N. Krasnova, Amber B. Hodges, Bruce Ladenheim, Raina Rhoades, Crystal G. Phillip, Angela Ceseňa, Ekaterina Ivanova, Christine F. Hohmann, Jean Lud Cadet

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 × 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.

Original languageEnglish (US)
Pages (from-to)160-165
Number of pages6
JournalNeuroscience Research
Volume65
Issue number2
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • Cortex
  • Dopamine
  • Methamphetamine
  • Neurotoxicity
  • Novelty-induced locomotor activity
  • Striatum

ASJC Scopus subject areas

  • General Neuroscience

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