Two kinds of mitogen-activated protein kinase phosphatases, MKP-1 and MKP-3, are differentially activated by acute and chronic methamphetamine treatment in the rat brain

Manabu Takaki, Hiroshi Ujike, Masafumi Kodama, Yasushi Takehisa, Kenji Nakata, Shigetoshi Kuroda

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Two functionally different MAP kinase phosphatases (MKPs) were investigated to clarify their roles in behavioral sensitization to methamphetamine (METH). MKP-1 mRNA levels increased substantially by about 60-300% in a range of brain regions, including several cortices, the striatum and thalamus 0.5-1 h after acute METH administration. After chronic METH administration its increase was less pronounced, but a more than 50% increase was still seen in the frontal cortex. MKP-1 protein levels also increased 3 h after acute or chronic METH administration. MKP-3 mRNA levels increased by about 30-50% in several cortices, the striatum and hippocampus 1 h after acute METH administration, but only in the hippocampus CA1 after chronic METH administration. Pre-treatment with the D1 dopamine receptor antagonist, SCH23390, attenuated the METH-induced increase of MKP-1 and MKP-3 mRNA in every brain region, while pre-treatment with the NMDA receptor antagonist, MK-801, attenuated it in some regions. These findings suggest that in METH-induced sensitization, MKP-1 and MKP-3 play important roles in the neural plastic modification in widespread brain regions in the earlier induction process, but in the later maintenance process, they do so only in restricted brain regions such as MKP-1 in the frontal cortices and MKP-3 in the hippocampus.

Original languageEnglish
Pages (from-to)679-688
Number of pages10
JournalJournal of Neurochemistry
Issue number3
Publication statusPublished - Nov 14 2001



  • Behavioral sensitization
  • Extracellular signal-regulated kinase
  • Methamphetamine
  • Mitogen-activated protein kinase phosphatase
  • Neural plasticity
  • Stress-activated protein kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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