A critical evaluation of the Gamma-Hydroxybutyrate (GHB) model of absence seizures

Venzi, Marcello, Di Giovanni, Giuseppe and Crunelli, Vincenzo ORCID: https://orcid.org/0000-0001-7154-9752 2015. A critical evaluation of the Gamma-Hydroxybutyrate (GHB) model of absence seizures. CNS Neuroscience & Therapeutics 21 (2) , pp. 123-140. 10.1111/cns.12337

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Abstract

Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the γ-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Cortex;EEG;GABA-B receptors;Hypnosis;Sedation;Thalamus
Publisher:	Wiley-Blackwell
ISSN:	1755-5930
Funders:	MRC, Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	17 September 2014
Last Modified:	20 May 2023 22:24
URI:	https://orca.cardiff.ac.uk/id/eprint/69646

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