Title:GABAB Receptors: are they Missing in Action in Focal Epilepsy Research?
Volume: 20
Issue: 9
Author(s): Massimo Avoli*Maxime Lévesque
Affiliation:
- Montreal Neurological Institute-Hospital and Departments of Neurology & Neurosurgery, McGill
University, Montreal, Canada H3A 2B4 QC
- Departments of Physiology, McGill University, Montreal, Canada H3A 2B4 QC
- Department of Experimental Medicine, Sapienza University of Rome,
00185 Rome, Italy
Keywords:
GABAB receptor signaling, focal epileptic disorders, in vitro epileptiform synchronization, ictal discharges, interictal discharges, limbic structures.
Abstract: GABA, the key inhibitory neurotransmitter in the adult forebrain, activates pre- and
postsynaptic receptors that have been categorized as GABAA, which directly open ligand-gated (or
receptor-operated) ion-channels, and GABAB, which are metabotropic since they operate through
second messengers. Over the last three decades, several studies have addressed the role of GABAB receptors in the pathophysiology of generalized and focal epileptic disorders. Here, we will address
their involvement in focal epileptic disorders by mainly reviewing in vitro studies that have shown:
(i) how either enhancing or decreasing GABAB receptor function can favour epileptiform synchronization
and thus ictogenesis, although with different features; (ii) the surprising ability of GABAB receptor
antagonism to disclose ictal-like activity when the excitatory ionotropic transmission is abolished;
and (iii) their contribution to controlling seizure-like discharges during repetitive electrical
stimuli delivered in limbic structures. In spite of this evidence, the role of GABAB receptor function
in focal epileptic disorders has been attracting less interest when compared to the numerous studies
that have addressed GABAA receptor signaling. Therefore, the main aim of our mini-review is to revive
interest in the function of GABAB receptors in focal epilepsy research.