Open AccessA Critical Evaluation of the Gamma‐Hydroxybutyrate ( GHB ) Model of Absence Seizures
Author(s) -
Venzi Marcello,
Di Giovanni Giuseppe,
Crunelli Vincenzo
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12337
Subject(s) - gamma hydroxybutyrate , neuroscience , neocortex , hypnosis , sedative , electroencephalography , psychology , neurocognitive , epilepsy , pharmacology , medicine , cognition , alternative medicine , pathology
Summary Typical absence seizures ( AS s) 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 AS s 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 AS s 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 AS s. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to AS s 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 AS s 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 AS s.