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

Journal of Pharmacological Sciences

Kiyofumi Yamada¹  Toshitaka Nabeshima¹  Hiroyuki Mizoguchi¹ 

[1] Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan

关键词: drugs of abuse;    matrix metalloproteinase;    tissue inhibitor of matrix metalloproteinase;    methamphetamine;    dopamine;   

DOI  :  10.1254/jphs.FM0070139

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(42)Cited-By(20)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.

【 授权许可】

Unknown