Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice

Hiroyuki Mizoguchi, Kiyofumi Yamada, Minae Niwa, Akihiro Mouri, Tomoko Mizuno, Yukihiro Noda, Atsumi Nitta, Shigeyoshi Itohara, Yoshiko Banno, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) function to remodel the pericellular environment. Their activation and regulation are associated with synaptic physiology and pathology. Here, we investigated whether MMP-2 and MMP-9 are involved in the rewarding effects of and sensitization to methamphetamine (METH) in animals, in which the remodelling of neural circuits may play a crucial role. Repeated METH treatment induced behavioural sensitization, which was accompanied by an increase in MMP-2 and MMP-9 activity in the brain. In MMP-2- and MMP-9-deficient mice [MMP-2-(-/-) and MMP-9-(-/-)], METH-induced behavioural sensitization and conditioned place preference, a measure of the rewarding effect, as well as METH-increased dopamine release in the nucleus accumbens (NAc) were attenuated compared with those in wild-type mice. In contrast, infusion of purified human MMP-2 into the NAc significantly potentiated the METH-increased dopamine release. The [3H]dopamine uptake into striatal synaptosomes was reduced in wild-type mice after repeated METH treatment, but METH-induced changes in [3H]dopamine uptake were significantly attenuated in MMP-2-(-/-) and MMP-9-(-/-) mice. These results suggest that both MMP-2 and MMP-9 play a crucial role in METH-induced behavioural sensitization and reward by regulating METH-induced dopamine release and uptake in the NAc.

Original languageEnglish
Pages (from-to)1579-1588
Number of pages10
JournalJournal of Neurochemistry
Volume100
Issue number6
DOIs
Publication statusPublished - 01-03-2007

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Methamphetamine
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Reward
Dopamine
Nucleus Accumbens
Corpus Striatum
Matrix Metalloproteinase Inhibitors
Synaptosomes
Physiology
Pathology
Brain
Animals
Chemical activation
Networks (circuits)

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Mizoguchi, Hiroyuki ; Yamada, Kiyofumi ; Niwa, Minae ; Mouri, Akihiro ; Mizuno, Tomoko ; Noda, Yukihiro ; Nitta, Atsumi ; Itohara, Shigeyoshi ; Banno, Yoshiko ; Nabeshima, Toshitaka. / Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice. In: Journal of Neurochemistry. 2007 ; Vol. 100, No. 6. pp. 1579-1588.
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Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice. / Mizoguchi, Hiroyuki; Yamada, Kiyofumi; Niwa, Minae; Mouri, Akihiro; Mizuno, Tomoko; Noda, Yukihiro; Nitta, Atsumi; Itohara, Shigeyoshi; Banno, Yoshiko; Nabeshima, Toshitaka.

In: Journal of Neurochemistry, Vol. 100, No. 6, 01.03.2007, p. 1579-1588.

Research output: Contribution to journalArticle

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T1 - Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice

AU - Mizoguchi, Hiroyuki

AU - Yamada, Kiyofumi

AU - Niwa, Minae

AU - Mouri, Akihiro

AU - Mizuno, Tomoko

AU - Noda, Yukihiro

AU - Nitta, Atsumi

AU - Itohara, Shigeyoshi

AU - Banno, Yoshiko

AU - Nabeshima, Toshitaka

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