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dc.contributor.authorJones, Bruce Edward
dc.date.accessioned2013-04-03T17:44:38Z
dc.date.available2013-04-03T17:44:38Z
dc.date.issued1992
dc.identifier.urihttp://hdl.handle.net/10713/2497
dc.descriptionUniversity of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 1992en_US
dc.description.abstractThe present study examined the effect of diazepam, pentobarbital, THIP (4,5,6,7-tetrahydroisoxazolo-(4,5c)-pyridone-3-d)), valproic acid and MK-801 treatment on metabolic, electrographic and behavioral components of a pilocarpine facilitated model of status epilepticus (pfSE). This study demonstrated that amygdala kindled rats pretreated with a non-convulsive dose of pilocarpine and electrically stimulated produce a stable seizure characterized by high-amplitude, fast-frequency EEG and increased ({dollar}\sp{lcub}14{rcub}{dollar}C) -2-deoxy-D-glucose ( ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG) uptake. Additionally, the present study demonstrated diazepam treatment during pfSE resulted in a dose-dependent decreased ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake. The somatosensory cortex appeared most sensitive whereas the amygdala, entorhinal cortex, reuniens nucleus, lateral septum and claustrum-endopiriform exhibited a resistance to diazepam with respect to ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake. The effect of diazepam was attenuated by the selective benzodiazepine antagonist Ro-15-1788. As with diazepam pentobarbital reduced regional ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake, however, the effect was not dose-dependent. THIP, valproic acid, and MK-801 did not alter the regional ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake pattern during pfSE. Except for pentobarbital no compound administered resulted in alterations in EEG. Therefore diazepam treatment was the only treatment which resulted in reductions in ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake without attenuation of EEG. Furthermore the data did not establish a link between potentiation of GABA receptor-mediated inhibition of neuronal activity and the effect of diazepam. However, there was evidence to suggest that kindling is important to the effect. This study also provides evidence that increased ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake was associated with high dose pilocarpine-induced SE. However, these data did not indicate that diazepam treatment resulted in reduced ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake in this particular model. In summary these data clearly demonstrate a dissociation of ({dollar}\sp{lcub}14{rcub}{dollar}C) -2DG uptake and electrical activity as a result of diazepam treatment. Furthermore these data suggest that diazepam mediates this effect through a specific receptor-mediated effect, however, no connection was established between the effect of diazepam and potentiation of GABA receptor-mediated inhibition of neuronal activity but it does appear as if kindling is necessary.en_US
dc.language.isoen_USen_US
dc.subjectBiology, Neuroscienceen_US
dc.subjectHealth Sciences, Pharmacologyen_US
dc.titlePharmacological treatment during status epilepticus: Metabolic and electrographic studiesen_US
dc.typedissertationen_US
dc.contributor.advisorButerbaugh, Gary G.
dc.identifier.ispublishedYes
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