Neuropsychotoxicity of abused drugs: involvement of matrix metalloproteinase-2 and -9 and tissue inhibitor of matrix metalloproteinase-2 in methamphetamine-induced behavioral sensitization and reward in rodents.
Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) function to remodel the pericellular environment. We have investigated the role of the MMP/TIMP system in methamphetamine (METH) dependence in rodents, in which the remodeling of neural circuits may be crucial. Repeated METH treatment induced behavioral sensitization, which was accompanied by an increase in MMP-2/-9/TIMP-2 activity in the brain. An antisense TIMP-2 oligonucleotide enhanced the sensitization, which was associated with a potentiation of the METH-induced release of dopamine in the nucleus accumbens (NAc). MMP-2/-9 inhibitors blocked the METH-induced behavioral sensitization and conditioned place preference (CPP), a measure of the rewarding effect of a drug, and reduced the METH-increased dopamine release in the NAc. In MMP-2- and MMP-9-deficient mice, METH-induced behavioral sensitization and CPP as well as dopamine release were attenuated. The MMP/TIMP system may be involved in METH-induced sensitization and reward by regulating extracellular dopamine levels.
Mizoguchi
Hiroyuki
H
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yamada
Kiyofumi
K
Nabeshima
Toshitaka
T
D019969:Amphetamine-Related Disorders / Q000201:enzymology* / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012201:Reward; D012377:Rodentia; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000697:Central Nervous System Stimulants; D061965:Matrix Metalloproteinase Inhibitors; D016376:Oligonucleotides, Antisense; D011480:Protease Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D008694:Methamphetamine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004298:Dopamine