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Localization and function of mammalian thalamic GABAB receptors - their role in absence epilepsy

Parry, Keith Philip; (1998) Localization and function of mammalian thalamic GABAB receptors - their role in absence epilepsy. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Intrathalamic administration of pertussis toxin was found to decrease the spike-and-wave discharge (SWD) of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). These injections of pertussis toxin were also found to reduce autoradiographically determined [3H]-GABA binding to GABAB binding sites, but not GABAA binding sites, in the thalamus. The results indicate that pertussis toxin-sensitive G-proteins are involved in the occurrence of SWD in GAERS, as well as providing further evidence for the involvement of thalamic GABAB receptors. The distribution of [3H]-GABA binding to GABAA and GABAB binding sites was determined autoradiographically in the absence epilepsy rat model Wistar Albino Glaxo, bred in Rijswijk (WAG/Rij) and the non-epileptic agouti rat strain (ACI). No difference between the strains was identified.[3H]-GABA binding to GABAB binding sites in the thalamus of the Rhesus monkey was also investigated. The results suggest that GABAB binding in thalamic nuclei is primarily associated with the level of input from the nucleus reticularis thalami (NRT), rather than the density of local circuit interneurones (LCN) and associations with input from the basal ganglia. An investigation of GABAB receptor-mediated modulation of cAMP and cGMP second messenger systems in vitro was undertaken. The ability of the GABAB receptor agonist, (-)baclofen, to inhibit forskolin-stimulated cAMP levels was demonstrated in rat thalamic slices. Nitric oxide donors, excitatory amino acid receptor agonists and veratridine stimulated an increase in the cGMP level of rat cerebellar slices. (-)Baclofen and the GABAB receptor antagonist, CGP 35348, were found to be incapable of modulating unstimulated and stimulated cGMP levels in rat cerebellar slices. Similarly veratridine increased the cGMP level of rat forebrain slices in a manner not altered by (-)baclofen or CGP 35348.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Localization and function of mammalian thalamic GABAB receptors - their role in absence epilepsy
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Absence; Epilepsy; GABAB; Localization; Mammalian; Thalamic
URI: https://discovery.ucl.ac.uk/id/eprint/10105137
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