Rapid cessation of focally induced generalized seizures in rats through microinfusion of lidocaine hydrochloride into the focus.

Abstract

An experimental animal model of complex partial seizures which become secondarily generalized is produced by microinfusion of the GABA antagonist bicuculline (BIC) into the deep prepiriform cortex (DPC) of rats. In the present study, we investigated the effects of microinfusion of the local anesthetic, lidocaine hydrochloride, directly into the BIC focus in the DPC and demonstrated that direct inactivation of the focus arrested a focal seizure that was in progress. A measure of the integrated amplitude of the electrocorticogram (ECoG) and behavioral seizure scores from unanesthetized and freely moving rats were used to address this question quantitatively. Microinfusion of 2% lidocaine hydrochloride into the BIC focus significantly reduced the integrated amplitude of the ECoG to levels that did not differ from baseline in either hemisphere (mean = 112% ipsilateral, 99% contralateral), whereas saline microinfusion had no effect (mean = 175% ipsilateral, 125% contralateral). Moreover, ECoG reductions after lidocaine were present as soon as the microinfusion was complete. Behaviorally, clonic seizure severity was assessed on a rating scale of 0-5. Lidocaine microinfusion significantly reduced the seizure scores to values not different from baseline during the first postinfusion measurement period (i.e., 30 s). Microinfusion of saline alone also significantly reduced behavioral seizure severity, although to a lesser degree and not as rapidly as lidocaine. This effect suggests the need for caution in interpretation and design of studies investigating the anticonvulsant effects of various pharmacologic agents when microinfusions are used.