start-ver=1.4
cd-journal=joma
no-vol=117
cd-vols=
no-issue=
article-no=
start-page=109038
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190930
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=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.
en-copyright=
kn-copyright=

en-aut-name=Ueno Hiroshi
en-aut-sei=Ueno
en-aut-mei= Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=Suemitsu Shunsuke
en-aut-sei=Suemitsu
en-aut-mei= Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=Murakami Shinji
en-aut-sei=Murakami
en-aut-mei= Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=Kitamura Naoya
en-aut-sei=Kitamura
en-aut-mei= Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=Wani Kenta
en-aut-sei=Wani
en-aut-mei= Kenta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=Takahashi Yu
en-aut-sei=Takahashi
en-aut-mei= Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=Matsumoto Yosuke
en-aut-sei=Matsumoto
en-aut-mei= Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Okamoto Motoi
en-aut-sei=Okamoto
en-aut-mei= Motoi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=Ishihara Takeshi
en-aut-sei=Ishihara
en-aut-mei= Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare
kn-affil=

affil-num=2
en-affil=Department of Psychiatry, Kawasaki Medical School
kn-affil=

affil-num=3
en-affil=Department of Psychiatry, Kawasaki Medical School
kn-affil=

affil-num=4
en-affil=Department of Psychiatry, Kawasaki Medical School
kn-affil=

affil-num=5
en-affil=Department of Psychiatry, Kawasaki Medical School
kn-affil=

affil-num=6
en-affil=Department of Psychiatry, Kawasaki Medical School
kn-affil=

affil-num=7
en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Psychiatry, Kawasaki Medical School
kn-affil=
en-keyword=Inhalation
kn-keyword=Inhalation
en-keyword=Dizocilpine
kn-keyword=Dizocilpine
en-keyword=MK-801
kn-keyword=MK-801
en-keyword=Mouse
kn-keyword=Mouse
en-keyword=Drug
kn-keyword=Drug
en-keyword=Schizophrenia
kn-keyword=Schizophrenia
END