Bilateral microinjections of vigabatrin in the central piriform cortex retard amygdala kindling in rats.
The piriform cortex (PC) is the largest region of the mammalian olfactory cortex with strong connections to limbic structures, including the amygdala, hippocampus, and entorhinal cortex. Various previous studies in rodents suggest that the PC might be very important in the development and maintenance of limbic kindling, i.e. a widely used model of temporal lobe epilepsy. GABAergic inhibition in the transition zone between the anterior and posterior PC, termed here central PC, seems to be particularly involved in the processes leading to progression of kindled seizures. This prompted us to study whether elevation of GABA levels in this subregion of the PC by bilateral microinjection of vigabatrin is capable of suppressing amygdala kindling. Rats were stimulated once daily until fully kindled (stage 5) seizures had developed. Vigabatrin (10 microg) was injected 24 h before the first stimulation as well as 6 h before the 5th and 10th stimulation, which approximately doubled the number of stimulations required for kindling development compared with controls. This marked retardation of kindling acquisition was predominantly due to a significant inhibition of the progression from stage 1 to stage 2 and stage 3 to stage 4 seizures, demonstrating that microinjection of vigabatrin into the central PC markedly inhibits the progression and secondary generalization of focal seizures emanating from the amygdala.
Schwabe
K
K
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
Ebert
U
U
Löscher
W
W
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004567:Electrodes, Implanted; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology; D020888:Vigabatrin / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D018755:GABA Agonists; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin