title: The anticonvulsant effects of SR 57227 on pentylenetetrazole-induced seizure in mice.
abstract: Recently, studies have shown that serotonin plays an important role in the control of seizure. However, the specific role of 5-HT receptor subtypes is not yet well described, in particular that of the 5-HT3 receptor. The present study was aimed to investigate the role of 5-HT3 receptor on the pentylenetetrazole (PTZ)-induced seizure in mice. Firstly, seizure latency was significantly prolonged by a 5-HT3 receptor agonist SR 57227 in a dose-dependent manner. Seizure score and mortality were also decreased by SR 57227 in PTZ-treated mice. Furthermore, these anticonvulsant effects of SR 57227 were inhibited by a 5-HT3 receptor antagonist ondansetron. However, ondansetron alone had no effect on seizure latency, seizure score or mortality at different doses. Immunohistochemical studies have also shown that c-Fos expression was significantly increased in hippocampus (dentate gyrus, CA1, CA3 and CA4) of PTZ-treated mice. Furthermore, c-Fos expression was significantly inhibited by ondansetron in mice treated with PTZ and SR 57227. An ELISA study showed that SR 57227 attenuated the PTZ-induced inhibitory effects of GABA levels in hippocampus and cortex, and the attenuated effects of SR 57227 were antagonized by ondansetron in hippocampus but not cortex. Our findings suggest that activation of 5-HT3 receptor by SR 57227, which plays an important role on the control of seizure induced by PTZ, may be related to GABA activity in hippocampus. Therefore, 5-HT3 receptor subtype is a potential target for the treatment of epilepsy.
authors.affiliation: Second hospital of Jilin University, Changchun, China; National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Bingjin
authors.initials: B
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: First hospital of Jilin University, Changchun, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Sun
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: Shao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Yunong
authors.initials: Y
authors.lastname: Song
authors.affiliation: China-Japan Union Hospital, Changchun, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Lv
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Dong
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Liu
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.affiliation: Second hospital of Jilin University, Changchun, China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Second hospital of Jilin University, Changchun, China; National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University, Changchun, China.
authors.forename: Ranji
authors.initials: R
authors.lastname: Cui
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D017294:Ondansetron / Q000494:pharmacology / Q000627:therapeutic use; D010433:Pentylenetetrazole; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*; D016019:Survival Analysis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D017294:Ondansetron; D005680:gamma-Aminobutyric Acid; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride; D010433:Pentylenetetrazole