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.
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
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Margolis
D M
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Chuang
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Dick
S R
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Weiss
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Post
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