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 kindling. We have investigated the effect of repeated lidocaine and cocaine administration on the phosphoinositide (PI) hydrolysis induced by batrachotoxin (BTX), a specific Na channel activator. Rats were injected with cocaine or saline daily for 6 days and PI hydrolysis was assayed in sliced frontal cortex. Cocaine treatment had no effect on BTX-induced PI hydrolysis while in vitro cocaine blocked the BTX effect. In a second experiment, rats received daily injections of lidocaine or saline. After a rat developed at least two seizures, it was sacrificed together with a rat receiving lidocaine injections which had never seized 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 greater in the HC than in the PC. Neither in vitro nor in vivo carbamazepine altered the effect of cocaine on BTX-induced PI hydrolysis. These results demonstrate that local anesthetic kindling does not alter PI hydrolysis coupled to Na channel or IBO activation.
Margolis
R L
RL
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
Chuang
D M
DM
Dick
D
D
Weiss
S R
SR
Post
R M
RM
D000818:Animals; D001496:Batrachotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects
D001496:Batrachotoxins; D010716:Phosphatidylinositols; D015222:Sodium Channels; D007051:Ibotenic Acid; D002220:Carbamazepine; D008012:Lidocaine; D003042:Cocaine