Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
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- Takashi Uehara
- Department of Neuropsychiatry, Kanazawa Medical University, Uchinada 920-0293, Japan
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- Masayoshi Kurachi
- Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Takashi Kondo
- Center for Low-Temperature Plasma Sciences, Nagoya University, Nagoya 464-8603, Japan
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- Hitoshi Abe
- Department of Applied Chemistry, Faculty of Engineering, University of Toyama, Toyama 930-8555, Japan
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- Hiroko Itoh
- Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
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- Tomiki Sumiyoshi
- Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan
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- Michio Suzuki
- Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
説明
<jats:p>Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.</jats:p>
収録刊行物
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- Journal of Personalized Medicine
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Journal of Personalized Medicine 12 (3), 366-, 2022-02-27
MDPI AG