Methamphetamine-induced neurotoxicity in BALB/c, DBA/2N and C57BL/6N mice

Taizo Kita, Shunchoru Paku, Masahiro Takahashi, Kaoru Kubo, George C. Wagner, Toshikatsu Nakashima

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46 Scopus citations


Repeated administration of methamphetamine (METH; 2 and 4 mg/kg, s.c. four times every 2 h) caused hyperthermia and a dose-dependent depletion of striatal dopamine levels 3 days after the METH-treatment in both BALB/cAnNCrj (BALB) and DBA/2NCrj (DBA) mice, but these responses were lower in C57BL/6NCrj (C57BL) mice. An acute decrease of striatal dopamine levels 30 min after the last injection of METH (4 mg/kg) was observed in both BALB and DBA mice, while an increase in dopamine was observed in C57BL mice. Striatal 3-methoxytyramine levels were drastically increased in both DBA and C57BL mice after this same treatment. Moreover, pretreatment with the superoxide dismutase inhibitor, diethyldithiocarbamate (200 mg/kg, i.p.) exacerbated the METH (4 mg/kg)-induced striatal dopamine-depletion in BALB mice. In addition, pretreatment with an inhibitor of poly(ADP-ribose) polymerase, benzamide (160 mg/kg, s.c.), significantly attenuated the METH (4 mg/kg)-induced striatal dopamine depletion in both BALB and DBA mice. These results suggest that both BALB and DBA mice possess a higher sensitivity to the METH-induced striatal dopaminergic neurotoxicity compared to C57BL mice. In addition, the striatal dopaminergic neurons of BALB mice may be more vulnerable to METH-induced oxidative stress as compared to that in C57BL mice. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1177-1184
Number of pages8
Issue number9
StatePublished - Sep 1998

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience


  • Dopamine
  • Hyperthermia
  • Methamphetamine
  • Neurotoxicity
  • Strain difference


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