Effects of neurotransmitter agonists on electrocortical activity in the rat kainate model of temporal lobe epilepsy and the modulatory action of basic fibroblast growth factor

Abstract

We used systemic kainic acid (KA) injection to investigate how the development of temporal lobe epilepsy and the associated network reorganization affect the electrocorticogram (ECoG) responses to various neurotransmitter agonists. Unrestrained rats chronically implanted with electrodes over somatosensory cortex and dorsal hippocampus and a cannula into the right lateral ventricle were used to investigate the ECoG frequency responses of intracerebroventricularly applied agonists (NMDA, clonidine, muscimol, and baclofen) at several types of receptors [NMDA, α 2-adrenergic (NE), GABA A, and GABA B, respectively] in KA-treated versus naïve animals. The ECoG was analyzed 2, 5, and 9 weeks after intraperitoneal injection of KA alone or in combination with basic fibroblast growth factor (bFGF, intracerebroventricularly). Within the first 5 weeks of KA injection, the ECoG power shifted towards the lower-frequency range. Concurrently, the electrographic responses to NMDA and clonidine were potentiated, whereas the ECoG effects mediated by GABA A and GABA B receptors remained largely unaffected. In control rats, bFGF strongly enhanced the electrographic NMDA responses. In sharp contrast, bFGF potently mitigated the abnormally increased NMDA sensitivity of epileptic rats, if applied 4 weeks post KA injection. These data suggest that upregulation and downregulation of the NMDA receptor-mediated effects on cortical activity might be a prominent feature of bFGF signaling in the intact and the damaged brain, respectively.