Abstracts

Gabapentin (1-(aminomethyl) cyclohexane acetic acid) is used clinically to treat partial as well as generalized seizures. While various experimental studies have investigated the effects of gabapentin in animal models of epilepsy, the precise mechanism of action of gabapentin against limbic seizures remains unclear. We therefore studied the efficacy of gabapentin during limbic status epilepticus induced by microinjection of kainic acid (KA) into the amygdala., Fourteen male Wistar rats (250 to 300 g) were prepared for experiments by a stereotactic operation performed with intraperitoneal pentobarbital anesthesia (40 mg/kg). A stainless steel screw was placed in contact with the dura overlying the left sensorimotor cortex (LCx). An additional screw was placed in the frontal sinus as a reference electrode. For microinjection, a stainless steel cannula with an inner needle guide was inserted into the left basolateral nucleus of the amygdala (LA). Bipolar depth electrodes were placed in the LA and the left dorsal hippocampus (LH). Seven days after the operation, 1.0 microg of KA was injected into the LA (n=8; KA group). In the control groups, 1.0 microl of PBS was injected into LA (n =6). In the KA group, 120 minutes after KA injection, while rats were exhibiting limbic status epilepticus, gabapentin was administered intraperitoneally (i.p.) at a dose of 100mg/kg. All rats were observed electrophysiologically and behaviorally over 7 days. The spike amplitude were measured in all records and values were expressed as persentage of controls., On the EEG in KA-injected rats, multiple spike discharges initially appeared in the LA 10 to 20 min after KA injection, and rapidly propagated to the LdH. Sixty minutes after KA injection, the seizure involved the LCx and resulted in limbic status epilepticus. Behaviorally, the rats showed bilateral facial twitching, mastication, and salivation. Ten to twenty minutes after gabapentin administration, the seizures in the LCx were selectively suppressed (spike amplitude; 10% of controls). The seizures in LA and LH also reduced (spike amplitude; approximately 30-50% of controls) In addition, behavioral seizure manifestations disappeared. In controls, the severe seizures continued., These results suggested that gabapentin suppresses secondary generalization of limbic seizures by a direct effect on the cerebral cortex., (Supported by Pfizer.)