EFFECT OF COCAINE, LIDOCAINE KINDLING AND CARBAMAZEPINE ON BATRACHOTOXIN-INDUCED PHOSPHOINOSITIDE HYDROLYSIS IN RAT-BRAIN SLICES

Repeated administration of a subconvulsant dose of a local anesthetic will eventually induce seizures, a phenomenon similar to electrical ki ndling. We have investigated the effect of repeated lidocaine and coca ine administration on the phosphoinositide (PI) hydrolysis induced by batrachotoxin (BTX), a specific Na channel activator. Rats were inject ed with cocaine or saline daily for 6 days and PI hydrolysis was assay ed in sliced frontal cortex. Cocaine treatment had no effect on BTX-in duced PI hydrolysis while in vitro cocaine blocked the BTX effect. In a second experiment, rats received daily injections of lidocaine or sa line. After a rat developed at least two seizures, it was sacrificed t ogether with a rat receiving lidocaine injections which had never seiz ed and a rat receiving saline injections. Basal, BTX and ibotenic acid (IBO; a glutamate receptor agonist)-stimulated PI hydrolysis did not differ among the three groups in slices of either hippocampus (HC) or piriform cortex (PC) though IBO-stimulated PI hydrolysis was much grea ter in the HC than in the PC. Neither in vitro nor in vivo carbamazepi ne altered the effect of cocaine on BTX-induced PI hydrolysis. These r esults demonstrate that local anesthetic kindling does not alter PI hy drolysis coupled to Na channel or IBO activation.