title: Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice.
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 [(3)H]dopamine uptake into striatal synaptosomes was reduced in wild-type mice after repeated METH treatment, but METH-induced changes in [(3)H]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.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Minae
authors.initials: M
authors.lastname: Niwa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mouri
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mizuno
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency*; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012201:Reward; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004298:Dopamine