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ID 115
file
creator
Hamamoto, Masahiro
Arai, Shigeaki
Kitayama, Shigeo
Kawahara, Michio
Dohi, Toshihiro
subject
Serotonin transporter
Convulsion
SSRI
Cocaine
Local anesthetics
NDC
Medical sciences
abstract
The present study examined whether the inhibition of serotonin transporters (SERT) contributes to cocaine- and other local anesthetics-induced convulsions, and which subtypes of 5-HT receptor are involved in the convulsions. For this purpose, cocaine, meprylcaine and lidocaine, all of which have different effects on SERT, were used as convulsants and the effects of serotonin reuptake inhibitors (SSRIs), specific agonists and antagonists for 5-HT receptor subtypes were evaluated in mice.Administration of SSRI, zimelidine, citalopram and fluoxetine, 5-HT2A,2C receptor agonist, R(-)-DOI and the 5-HT2C receptor agonists, mCPP and MK212 resulted in a marked increase in incidence of convulsions and a reduction in the threshold of lidocaine-induced convulsions, while the 5-HT2B receptor agonist, BW723C86, had little influence. On the other hand, SSRI did not affect the measured parameters in meprylcaine- and cocaine-induced convulsions. R(-)-DOI, mCPP and MK212 reduced the threshold of meprylcaine or cocaine with less extent than the reduction of lidocaine threshold. Incidence of cocaine- and meprylcaine-induced convulsions were significantly reduced by 5-HT2A,2B,2C antagonist, LY-53857 and 5-HT2C antagonist, RS 102221. The threshold of cocaine and meprylcaine was significantly increased by both antagonists. 5-HT2A antagonists MDL-11,939 and ketanserin, and 5-HT2B antagonist SB-204741 except at high doses had little effect on cocaine- and meprylcaine-induced convulsions. None of these antagonists altered the parameters of lidocaine-induced convulsions. Pretreatment with fluoxetine but not citalopram increased the plasma concentration of lidocaine. These results suggest that the increase of serotonergic neuronal activity through 5-HT2C receptor stimulation was responsible for increased activity of local anesthetics-induced convulsions and support the involvement of this mechanism in cocaine- and meprylcaine- but not in lidocaine- induced convulsions through their direct inhibitory action on central SERT.
journal title
Brain Research
volume
Volume 1057
issue
Issue 1-2
start page
153
end page
160
date of issued
2005-09-28
publisher
Elsevier B.V
issn
0361-0713
ncid
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) 2005 Elsevier B.V
relation is version of URL
http://dx.doi.org/10.1016/j.brainres.2005.07.049
department
Graduate School of Biomedical Science