Abstract
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.
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Acknowledgements
This study was supported in part by grants from the Minister of Education, Culture, Sports, Science, and Technology of Japan (KH), the Ministry of Health, Labor and Welfare of Japan (KH), and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institutes of Biomedical Innovation (KH). We thank Dr Nori Takei (Department of Psychiatry, Hamamatsu University School of Medicine) for his valuable suggestion on statistical analysis.
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Zhang, L., Shirayama, Y., Iyo, M. et al. Minocycline Attenuates Hyperlocomotion and Prepulse Inhibition Deficits in Mice after Administration of the NMDA Receptor Antagonist Dizocilpine. Neuropsychopharmacol 32, 2004–2010 (2007). https://doi.org/10.1038/sj.npp.1301313
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DOI: https://doi.org/10.1038/sj.npp.1301313
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