Spontaneous epileptic activity resembling spike wave discharges (SWD) characteristic of Generalized Absence (GA) epilepsy was induced in rat thalamocortical (TC) slices by incubating the slices in low-Mg2- artificial cerebrospinal fluid (ACSF) Extracellular field potentials were recorded in the cortex and thalamus to determine the effects of the broad spectrum metabotropic glutamate receptor (mGluR) agonist, trans- (1S, 3R)-1-Amino-1, 3-cyclopentanedicarboxylic acid (ACPD), ACPD elicited concentration dependent effects on the duration of SWD. At 1 μM ACPD (n=3) there were no significant changes in duration of activity. At 20 μM, 11 of 13 slices displayed a decrease in duration of activity (mean = 40.47 ± 5.07). In all cases, 200 μM ACPD (n=6) transformed SWD into single spike activity. Furthermore, the broad spectrum mGluR antagonist, (S)-α-Methyl-4-carboxyphenlglycine ((S)-MCPG), when pre-applied to TC slices at 500. μM followed by co-application with 200 μM ACPD (n=3), prevented SWD from switching into single spike activity.
To determine the site of action of the mGluR agonist. experiments involving regional perfusion of 200 μM ACPD to the cortex (n=3) and thalamus (n=4) were conducted. mGluR activation in the cortex was unable to block SWD, while perfusion of the mGluR agonist to the thalamus transformed SWD into single spikes on all occasions. mGluRs may provide an alternative therapeutic target for the pharmacological treatment of GA epilepsy.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-6391 |
| Date | 01 January 1998 |
| Creators | Sharma, Joy Vashisht |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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