Improvement by minocycline of methamphetamine-induced impairment of recognition memory in mice

被引:82
作者
Mizoguchi, Hiroyuki [4 ,5 ]
Takuma, Kazuhiro [5 ]
Fukakusa, Ayumi [5 ]
Ito, Yukio [5 ]
Nakatani, Akiko [5 ]
Ibi, Daisuke [5 ]
Kim, Hyoung-Chun [3 ]
Yamada, Kiyofumi [1 ,2 ,5 ]
机构
[1] Nagoya Univ, Grad Sch Med, Hosp Pharm, Showa Ku, Nagoya, Aichi 4668560, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol, Showa Ku, Nagoya, Aichi 4668560, Japan
[3] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea
[4] Nagoya Univ, Inst Environm Med, Futurist Environm Simulat Ctr Res, Chikusa Ku, Nagoya, Aichi 4648601, Japan
[5] Kanazawa Univ, Grad Sch Nat Sci & Technol, Div Life Sci, Lab Neuropsychopharmacol, Kanazawa, Ishikawa 9201192, Japan
基金
日本学术振兴会;
关键词
minocycline; methamphetamine; schizophrenia; memory; prefrontal cortex;
D O I
10.1007/s00213-007-0955-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Introduction Cognitive deficits are a core feature of patients with schizophrenia and methamphetamine (METH) psychosis. We have recently found that repeated METH treatment (1 mg/kg, s.c.) in mice, which induces behavioral sensitization, impairs long-term recognition memory in a novel object recognition test (NORT) and that the impairment is ameliorated by clozapine, but not haloperidol. Recent studies indicate that minocycline, a second-generation tetracycline, has potent neuroprotective effects in various animal models of neurological diseases. Objectives In the present study, we investigated the effect of minocycline on learning and memory in the NORT and behavioral sensitization in mice that had been administered METH for 7 days. Results When minocycline (20-40 mg/kg) was administered intraperitoneally once a day for seven consecutive days to mice that had previously been treated with METH for 7 days, it ameliorated the METH-induced impairment of recognition memory in a dose-dependent manner, although the same treatment with minocycline had no effect on behavioral sensitization to METH. The administration of minocycline, together with METH, inhibited the development of METH-induced behavioral sensitization. The improvement in memory caused by minocycline was associated with an amelioration of the novelty-induced activation of extracellular signal-regulated kinase 1/2 in the prefrontal cortex of METH-treated mice. Conclusions These results suggest that minocycline is useful for the treatment of cognitive deficits in patients with METH psychosis or schizophrenia.
引用
收藏
页码:233 / 241
页数:9
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