A Critical Evaluation of the Gamma-Hydroxybutyrate (GHB) Model of Absence Seizures.

A Critical Evaluation of the Gamma-Hydroxybutyrate (GHB) Model of Absence Seizures.
CNS Neurosci Ther. 2014 Nov 18;
Authors: Venzi M, Di Giovanni G, Crunelli V
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 o...

Source: CNS Neuroscience and Therapeutics - November 18, 2014 Category: Neuroscience Authors: Venzi M, Di Giovanni G, Crunelli V Tags: CNS Neurosci Ther Source Type: research