Kenshi Takechi1, Akinori Fujiwara, Yusuke Watanabe, Chiaki Kamei. 1. Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Okayama 700-8530, Japan.
Abstract
PURPOSE: The present study was undertaken to clarify the participation of the GABA-ergic system in epileptogenic activity induced by teicoplanin. METHODS: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and stainless steel electrodes were implanted into the frontal cortex (FCOR), hippocampus (HPC) and amygdala (AMG). Behavioral and electroencephalographic (EEG) changes were observed for 60min following teicoplanin intracerebroventricular (i.c.v.) injection. RESULTS: I.c.v. injection of teicoplanin caused dose-related behavioral and EEG seizures. MK-801 (N-methyl-d-aspartate receptors antagonist) had no significant influence on either behavioral or EEG seizures induced by teicoplanin (500microg, i.c.v.). On the other hand, NNC-711 (GABA transporters inhibitor) dose-dependently antagonized behavioral and EEG seizures induced by teicoplanin (500microg, i.c.v.). The inhibitory effect of NNC-711 (10mg/kg, i.p.) on teicoplanin-induced epileptogenic activity was antagonized by bicuculline (GABA(A) receptor antagonist) but not by TPMPA (GABA(C) receptor antagonist). CONCLUSIONS: It is reasonable to presume that teicoplanin-induced epileptogenic seizures are closely related with GABA-ergic mechanisms through GABA(A) receptors rather than GABA(C) receptors.
PURPOSE: The present study was undertaken to clarify the participation of the GABA-ergic system in epileptogenic activity induced by teicoplanin. METHODS: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and stainless steel electrodes were implanted into the frontal cortex (FCOR), hippocampus (HPC) and amygdala (AMG). Behavioral and electroencephalographic (EEG) changes were observed for 60min following teicoplanin intracerebroventricular (i.c.v.) injection. RESULTS: I.c.v. injection of teicoplanin caused dose-related behavioral and EEG seizures. MK-801 (N-methyl-d-aspartate receptors antagonist) had no significant influence on either behavioral or EEG seizures induced by teicoplanin (500microg, i.c.v.). On the other hand, NNC-711 (GABA transporters inhibitor) dose-dependently antagonized behavioral and EEG seizures induced by teicoplanin (500microg, i.c.v.). The inhibitory effect of NNC-711 (10mg/kg, i.p.) on teicoplanin-induced epileptogenic activity was antagonized by bicuculline (GABA(A) receptor antagonist) but not by TPMPA (GABA(C) receptor antagonist). CONCLUSIONS: It is reasonable to presume that teicoplanin-induced epileptogenic seizures are closely related with GABA-ergic mechanisms through GABA(A) receptors rather than GABA(C) receptors.
Authors: Candy Flores-Gracia; Avril Nuche-Bricaire; Minerva Crespo-Ramírez; Ricardo Miledi; Kjell Fuxe; Miguel Pérez de la Mora Journal: Psychopharmacology (Berl) Date: 2010-08-06 Impact factor: 4.530