Benzodiazepine receptor inverse agonist-induced kindling of rats alters learning and glutamate binding.
Kindling, recognized as a model of epilepsy, can be obtained by applications of repeated nonconvulsive stimulations that finally lead to generalized seizures. Epileptics often show cognitive impairments. The present work analyzed the learning performance of male Wistar rats kindled with a convulsant inverse agonist of the GABA(A)-benzodiazepine receptor complex, methyl beta-carboline-3-carboxylate (beta-CCM). This compound is also known to have an action on learning processes. It was thus interesting to verify if beta-CCM kindling had the same impairing action on learning as other kindling agents, such as pentylenetetrazol (PTZ). A two-way active-avoidance shuttle-box learning task was chosen, because a deficit was found after PTZ kindling in this learning model. On the other hand, hippocampal glutamate binding, has previously been shown to be modified by both seizures and learning. Thus, the level of glutamate binding was also measured in the present study. Results showed that fully kindled rats had poorer learning performance after the third day of test than controls or not fully kindled animals. L-[3H] glutamate binding to hippocampal membrane fractions of the fully kindled animals was significantly higher when compared with controls, whereas L-[3H] glutamate binding of not fully kindled subjects did not differ from that of controls. Neuronal plasticity changes are a possible explanation for the correlation between kindling, learning deficits, and increased glutamate binding.
Rössler
A S
AS
Hôpital Pitié-Salpêtrière, UMR 7593, CNRS, 91 Boulevard Hôpital, 75634 Cedex 13, Paris, France. rossler@ext.jussieu.fr
Schröder
H
H
Dodd
R H
RH
Chapouthier
G
G
Grecksch
G
G
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D007858:Learning / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002243:Carbolines; D058785:GABA-A Receptor Agonists; D018698:Glutamic Acid; C036150:beta-carboline-3-carboxylic acid methyl ester