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Ueno, Hiroshi Department of Medical Technology, Kawasaki University of Medical Welfare
Suemitsu, Shunsuke Department of Psychiatry, Kawasaki Medical School
Murakami, Shinji Department of Psychiatry, Kawasaki Medical School
Kitamura, Naoya Department of Psychiatry, Kawasaki Medical School
Wani, Kenta Department of Psychiatry, Kawasaki Medical School
Takahashi, Yu Department of Psychiatry, Kawasaki Medical School
Matsumoto, Yosuke Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Okamoto, Motoi Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Ishihara, Takeshi Department of Psychiatry, Kawasaki Medical School
The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801–induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders.
Biomedicine & Pharmacotherapy
© 2019 The Authors. Published by Elsevier Masson SAS.
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Hiroshi Ueno, Shunsuke Suemitsu, Shinji Murakami, Naoya Kitamura, Kenta Wani, Yu Takahashi, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara, Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice, Biomedicine & Pharmacotherapy, Volume 117,2019, 109038,ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2019.109038.