Cortical and hippocampal EEG effects of neurotransmitter agonists in spontaneously hypertensive vs. kainate-treated rats.

To analyze mediatory mechanisms underlying attention-deficit hyperactivity disorder (ADHD) and their association with epilepsy, the electroencephalogram (EEG) responses to various centrally applied neurotransmitter agonists were studied in spontaneously hypertensive (SH), kainate-treated (KA), and normotensive (control) rats, with chronically implanted electrodes into the frontal cortex and hippocampus and a cannula into the lateral cerebral ventricle. In SH rats, the baseline EEG showed increased delta and beta2 activity in the hippocampus and decreased alpha/beta1 activity in both brain areas. In KA rats, these delta and alpha/beta1 effects were observed 2 weeks post-kainate, while the beta2 activity increase occurred after 5 weeks in the hippocampus and, to a greater extent, 9 weeks post-injection in both brain areas. In SH rats, NMDA increased delta and decreased alpha/beta1 activity, similar to KA rats 5 weeks post-injection. In SH rats, clonidine augmented theta/beta2 increase in the cortex and alpha suppression in both brain areas, in parallel with induction of beta2 activity in the hippocampus. These beta2 effects were observed 5 and 9 weeks post-kainate. In SH rats, baclofen produced robust delta/theta enhancement and alpha/beta1 suppression in both brain areas, with additional beta2 activity increase in the hippocampus, while muscimol was ineffective in both groups of rats. In KA rats, EEG responses to GABA agonists were similar to those in control. Our results demonstrate sensitization of NMDA receptors and α2-adrenoceptors both in SH and KA rats and that of GABAb receptors specifically in SH rats.

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.

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, alpha2-adrenergic (NE), GABAA, and GABAB, 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 GABAA and GABAB 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.

EEG modifications in the cortex and striatum after dopaminergic priming in the 6-hydroxydopamine rat model of Parkinson's disease.

In rats bearing a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, a single administration of a dopamine receptor agonist (priming) sensitizes the behavioral motor responses to a dopaminergic agonist, administered 3 days after priming. In this study, changes in the electroencephalogram (EEG) frequency spectra were evaluated during priming in unilaterally 6-OHDA-lesioned rats, implanted bilaterally with electrodes both in the somatosensory cortex and striatum. Two weeks after 6-OHDA lesion, rats were primed with apomorphine (0.2 mg/kg) and received a challenge with the D(1) agonist SKF 38393 (3 mg/kg) 3 days later. 6-OHDA lesion modified the EEG pattern mainly in the beta(1) frequency band, in both cortex and striatum. Apomorphine priming produced a power decrease in the beta(1) frequency band, more pronounced in the cortex than in the striatum, as compared to saline-treated rats. Antagonism of NMDA receptor with MK-801, a treatment known to block the development of priming, increased apomorphine inhibitory effect mainly in the striatum, producing the same degree of inhibition in the two structures. Administration of SKF 38393, 3 days after priming, caused a power decrease in beta(1) frequency band of the cortex and striatum, which was more pronounced in apomorphine-primed as compared to drug-naive rats. The inhibitory effect of SKF 38393 was enhanced in rats primed with MK-801 plus apomorphine, particularly in the striatum. The results of this study suggest that long-term changes in the electrical activity of cortex and striatum after priming, might contribute to the development of the behavioral sensitization observed after priming. Development of priming might be related to the degree and cortical/striatal ratio of EEG power inhibition produced by dopamine agonists.