Long-lasting potentiation effects induced in rats by kindling with an inverse agonist of the benzodiazepine receptor.
The present work analyzed the changes in evoked field potentials of freely moving rats after kindling induced by a convulsant inverse agonist of the GABA(A)-benzodiazepine receptor complex, methyl beta-carboline-3-carboxylate (beta-CCM). Two doses of beta-CCM (2 mg/kg and 4 mg/kg) were used. In kindled and control animals, a stimulating electrode was implanted in the perforant pathway and a recording electrode in the dentate gyrus. Results showed that, after an acutely injected dose of 20 mg/kg pentylenetetrazol (PTZ), all kindled animals showed a decrease in population spike amplitude after 20 min. After 60 min, only fully kindled rats showed a long-lasting potentiation, also visible up to 24 h later, as compared to controls or nonkindled animals. Changes in glutamate and GABA receptor binding measured in previous experiments may explain this potentiation effect observed in fully kindled rats.
Rössler
Anne-Sophie
AS
UMR 7593 CNRS, Medical Faculty Pitié-Salpêtrière, 75013 Paris, France. chapout@ext.jussieu.fr
Rüthrich
Heinz
H
Krug
Manfred
M
Dodd
Robert H
RH
Chapouthier
Georges
G
Grecksch
Gisela
G
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D018891:Dentate Gyrus / Q000502:physiology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005071:Evoked Potentials / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D019580:Perforant Pathway / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
D002243:Carbolines; D003292:Convulsants; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; C036150:beta-carboline-3-carboxylic acid methyl ester; D010433:Pentylenetetrazole