Participation of GABA-ergic system in epileptogenic activity induced by teicoplanin in mice

SummaryPurposeThe present study was undertaken to clarify the participation of the GABA-ergic system in epileptogenic activity induced by teicoplanin.MethodsUnder 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 60 min following teicoplanin intracerebroventricular (i.c.v.) injection.ResultsI.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 (500 μg, i.c.v.). On the other hand, NNC-711 (GABA transporters inhibitor) dose-dependently antagonized behavioral and EEG seizures induced by teicoplanin (500 μg, i.c.v.). The inhibitory effect of NNC-711 (10 mg/kg, i.p.) on teicoplanin-induced epileptogenic activity was antagonized by bicuculline (GABAA receptor antagonist) but not by TPMPA (GABAC receptor antagonist).ConclusionsIt is reasonable to presume that teicoplanin-induced epileptogenic seizures are closely related with GABA-ergic mechanisms through GABAA receptors rather than GABAC receptors.