Seizure, neurotransmitter release, and gene expression are closely related in the striatum of 4-aminopyridine-treated rats.

The present experiments aimed to compare the length of seizure activity with the time-related increase of transmitter release and the induction of c-fos gene expression in the striatum of the rat. Anesthetized Wistar rats were intraperitoneally treated with 7 mg/kg 4-aminopyridine, and the transmitter levels in the striatum were measured by means of in vivo microdialysis, 30, 60, 90, 120, and 150 min following the treatment. Striatal and neocortical electric activity was monitored with depth and surface electrodes, respectively. The expression level of the c-fos gene was estimated by counting the striatal c-fos-immunostained cell nuclei at the time intervals of the microdialysis. 4-aminopyridine elicited high-frequency seizure discharges in the EEG and significantly increased glutamate, aspartate, GABA, serotonin, noradrenaline, and dopamine levels in the extracellular dialysates. The number of c-fos-stained cell nuclei in the striatum displayed a prolonged increase, showing significantly elevated numbers throughout the experiment. The increase of c-fos expression in time correlated best with the increase of glutamate release, which was also significantly elevated at every sampling time. The GABA release, culminating at 60 min after the seizure onset, correlated best with the cessation of the electrographic seizure. Aspartate, norepinephrine, serotonin, and dopamine displayed transient but significant elevations. We conclude that glutamate plays the essential role (most probably through ionotropic and metabotropic receptors) in the extracellular signaling, which eventually leads to intracellular cascades and c-fos gene expression in the striatum during convulsions.