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ID 113
file
creator
Arai, Shigeaki
Kitayama, Shigeo
Kumagai, Kei
Kumagai, Michiko
Dohi, Toshihiro
subject
Inhibition of monoamine transporters
Seizure
Kindling
Local anesthetics
Cocaine
NDC
Medical sciences
abstract
Involvement of chronic inhibition of monoamine transporters (MAT) in the brain concerning the sensitization of cocaine- and local anesthetic-induced seizures was studied in mice. Repeated administration of subconvulsive doses of meprylcaine as well as cocaine, both of which inhibit MAT, but not lidocaine, which does not inhibit MAT, increased seizure activity and produced sensitization to other local anesthetics. Effects of 5 daily treatments of monoamine transporter inhibitors on lidocaine-induced convulsions were examined 2 or 3 days after the last dose of the inhibitors. The daily treatments of GBR 12935, a specific inhibitor of dopamine uptake, significantly increased the incidence and the intensity of lidocaine-induced convulsions at 20 mg/kg and decreased the threshold of the convulsions. The daily treatments of desipramine and maprotiline, selective norepinephrine uptake inhibitors, markedly increased the incidence and intensity of lidocaine-induced convulsions, and decreased the threshold with dose-dependent manner between 5 and 20 mg/kg. The daily treatments of citaloplam, a selective serotonin uptake inhibitor, 10 and 20 mg/kg, produced no significant increase in the incidence or intensity of lidocaine-induced convulsions but decreased the threshold of the convulsions. These results suggest that the chronic intermittent inhibition of monoamine uptake increases susceptibility to cocaine- and local anesthetic-induced seizures, and a norepinephrine transporter is an integral component of this sensitization.
journal title
Brain research
volume
Volume 964
issue
Issue 1
start page
83
end page
90
date of issued
2003-02-21
publisher
Elsevier Science B.V.
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2002 Elsevier Science B.V.
relation is version of URL
http://dx.doi.org/10.1016/S0006-8993(02)04068-4
department
Graduate School of Biomedical Science