Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine
Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine
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DOI：
10.1038/sj.npp.1301313
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发表时间：
2007-09-01
影响因子：
7.6
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
--
作者：
Zhang, Lin;Shirayama, Yukihiko;Hashimoto, Kenji
本研究旨在检查第二代抗生素药物米诺环素是否能减轻给予N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（+）-MK-801（地佐环平）后小鼠的行为变化（例如，急性过度运动和前脉冲抑制（PPI）缺陷）。二甲胺四环素（40 mg/kg）预处理可显著减弱地佐环平（0.1 mg/kg）诱导的过度运动。此外，地佐环平（0.1 mg/kg）单次给药后的PPI赤字与米诺环素（10，20或40 mg/kg）的预处理，以剂量依赖性的方式衰减。此外，在自由活动的小鼠中的体内微透析研究显示，用米诺环素（40 mg/kg，i. p.）显著减弱了地佐环平（0.1 mg/kg）给药后额叶皮层和纹状体细胞外多巴胺（DA）水平的增加，表明米诺环素对地佐环平诱导的DA释放的抑制可能至少部分涉及米诺环素对地佐环平诱导的小鼠行为变化的作用机制。这些结果表明，米诺环素可以减轻NMDA受体拮抗剂地佐环平给药后小鼠的行为变化。因此，米诺环素有可能成为精神分裂症的潜在治疗药物。
The present study was undertaken to examine whether the second generation antibiotic drug minocycline attenuates behavioral changes (eg, acute hyperlocomotion and prepulse inhibition ( PPI) deficits) in mice after the administration of the N-methyl-D-aspartate ( NMDA) receptor antagonist (+)-MK-801 ( dizocilpine). Dizocilpine (0.1 mg/kg)-induced hyperlocomotion was significantly attenuated by pretreatment with minocycline ( 40 mg/kg). Furthermore, the PPI deficits after a single administration of dizocilpine ( 0.1 mg/kg) were attenuated by pretreatment with minocycline ( 10, 20, or 40 mg/kg), in a dose-dependent manner. Moreover, in vivo microdialysis study in the free-moving mice revealed that pretreatment with minocycline ( 40 mg/kg, i.p.) significantly attenuated the increase of extracellular dopamine (DA) levels in the frontal cortex and striatum after administration of dizocilpine ( 0.1 mg/kg), suggesting that the inhibition of dizocilpine-induced DA release by minocycline may, at least in part, be implicated in the mechanism of action of minocycline with respect to dizocilpine-induced behavioral changes in mice. These findings suggest that minocycline could attenuate behavioral changes in mice after the administration of the NMDA receptor antagonist dizocilpine. Therefore, it is possible that minocycline would be a potential therapeutic drug for schizophrenia.