Participation of GABA-ergic system in epileptogenic activity induced by teicoplanin in mice.
OBJECTIVE
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.
Takechi
Kenshi
K
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Okayama 700-8530, Japan.
Fujiwara
Akinori
A
Watanabe
Yusuke
Y
Kamei
Chiaki
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001640:Bicuculline / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D018756:GABA Antagonists / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009557:Nipecotic Acids / Q000627:therapeutic use; D010091:Oximes / Q000627:therapeutic use; D010721:Phosphinic Acids / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D017334:Teicoplanin / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009557:Nipecotic Acids; D010091:Oximes; D010721:Phosphinic Acids; D011725:Pyridines; C078793:NNC 711; D005680:gamma-Aminobutyric Acid; D017334:Teicoplanin; D016291:Dizocilpine Maleate; D001640:Bicuculline