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Role of matrix metalloproteinase and tissue inhibitor of MMP in methamphetamine‐induced behavioral sensitization and reward: implications for dopamine receptor down‐regulation and dopamine release
Author(s) -
Mizoguchi Hiroyuki,
Yamada Kiyofumi,
Mouri Akihiro,
Niwa Minae,
Mizuno Tomoko,
Noda Yukihiro,
Nitta Atsumi,
Itohara Shigeyoshi,
Banno Yoshiko,
Nabeshima Toshitaka
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04623.x
Subject(s) - meth , methamphetamine , nucleus accumbens , dopamine , sensitization , dopamine receptor d1 , agonist , chemistry , pharmacology , conditioned place preference , dopamine receptor d2 , dopamine uptake inhibitors , receptor , endocrinology , medicine , neuroscience , biology , biochemistry , monomer , organic chemistry , acrylate , polymer
Matrix metalloproteinases (MMPs) and its inhibitors (TIMPs) function to remodel the pericellular environment. We have demonstrated that methamphetamine (METH)‐induced behavioral sensitization and reward were markedly attenuated in MMP‐2‐ and MMP‐9 deficient [MMP‐2‐(−/−) and MMP‐9‐(−/−)] mice compared with those in wild‐type mice, suggesting that METH‐induced expression of MMP‐2 and MMP‐9 in the brain plays a role in the development of METH‐induced sensitization and reward. In the present study, we investigated the changes in TIMP‐2 expression in the brain after repeated METH treatment. Furthermore, we studied a role of MMP/TIMP system in METH‐induced behavioral changes and dopamine neurotransmission. Repeated METH treatment induced behavioral sensitization, which was accompanied by an increase in TIMP‐2 expression. Antisense TIMP‐2 oligonucleotide (TIMP‐AS) treatment enhanced the sensitization, which was associated with the potentiation of METH‐induced dopamine release in the nucleus accumbens (NAc). On the other hand, MMP‐2/‐9 inhibitors blocked the METH‐induced behavioral sensitization and conditioned place preference, a measure of the rewarding effect, and reduced the METH‐increased dopamine release in the NAc. Dopamine receptor agonist‐stimulated [ 35 S]GTPγS binding was reduced in the frontal cortex of sensitized rats. TIMP‐AS treatment potentiated, while MMP‐2/‐9 inhibitor attenuated, the reduction of dopamine D2 receptor agonist‐stimulated [ 35 S]GTPγS binding. Repeated METH treatment also reduced dopamine D2 receptor agonist‐stimulated [ 35 S]GTPγS binding in wild‐type mice, but such changes were significantly attenuated in MMP‐2‐(−/−) and MMP‐9‐(−/−) mice. These results suggest that the MMP/TIMP system is involved in METH‐induced behavioral sensitization and reward, by regulating dopamine release and receptor signaling.