Effect of cocaine and lidocaine on the development of kindled seizures

Abstract

The effect of a subconvulsive dose of cocaine or lidocaine on the development of kindling was studied in male Long-Evans rats. Animals were divided into three groups and kindled by daily electrical stimulation of the pyriform cortex. Fifteen minutes before each stimulation each animal received an intraperitoneal injection of either saline, 20 mg/kg cocaine hydrochloride, or 20 mg/kg lidocaine hydrochloride. Following kindling the drug treatment was discontinued and the transfer of kindling to a nondrug state was assessed by test stimulations given 2, 6, and 48 days after the last of day kindling. Both cocaine and lidocaine dramatically accelerated the development of kindling. Furthermore, the duration of clonus at kindling criterion was significantly longer in lidocaine-treated animals than in animals treated with saline, and the onset of clonus in cocaine-treated animals occurred significantly sooner after stimulation. However, this performance did not transfer fully to the nondrug state, with some animals failing to exhibit clonus. Among those animals exhibiting clonus at nondrug tests, afterdischarge duration was significantly higher in cocaine-treated than in saline-treated animals, but clonus duration was no longer elevated in lidocaine-treated animals, and the latency to clonus rose dramatically in animals previously treated with either cocaine or lidocaine. These results indicate that a subconvulsive dose of cocaine of lidocaine can facilitate the development of kindling when the drug is active at the time of electrical stimulation, apparently by means of the local anesthetic action shared by the two drugs. The kindling produced in this fashion is not entirely equivalent to kindling produced by electrical stimulation alone. In animals kindled under the influence of local anesthetic, the afterdischarge at the site of stimulation is expressed at least as strongly in the absence of the drugs as in their presence, but spread of seizure activity to other areas of the brain, as reflected by the occurence and latency of clonus, appears to have been temporarily enhanced by the drugs and is weakened in their absence.