Gamma-hydroxybutyrate promotes oscillatory activity of rat and cat thalamocortical neurons by a tonic GABAB receptor-mediated hyperpolarization

Generalized Epileptic Disorders: An Update

“…Additional evidence in favor of a role of GABA mechanisms in the generation of spikeand-wave discharges comes from work with ␥-hydroxybutyrate, a drug that causes behavioral and EEG alterations similar to those seen during absence attacks (83,84). ␥-Hydroxybutyrate activates GABA B receptors, causing steady membrane hyperpolarization, which leads to deinactivation of T-type Ca 2+ channels (85). The result is, therefore, oscillatory activity and rhythmic action-potential burst firing in thalamocortical neurons.…”

Pertussis Toxin Lesions of the Rat Substantia Nigra Block the Inhibitory Effects of the γ-Hydroxybutyrate Agent, S(-)HA-966 without Affecting the Basal Firing Properties of Dopamine Neurons

“…However, recent evidence suggests that the effects of the compound are mediated through an interaction with GABA B receptors. For example, GHBinduced increases in oscillatory firing of thalamocortical neurons together with the resultant "spike and wave" EEG discharge characteristic of absence seizures are blocked by the GABA B receptor antagonist, CGP 35348 (Snead 1992;Williams et al 1995). Changes in the firing rate and discharge pattern of nigral DA neurons following GHB are also blocked by systemic administration of CGP-35348 (Engberg and Nissbrandt 1993;Erhardt et al 1998) as are the increases in DA levels and synthesis in the forebrain (Waldmeier 1991;Nissbrandt and Engberg 1996).…”

“…Pertussis toxin (PT), a compound that inactivates G i/o proteins via ADP-ribosylation, blocks the postsynaptic actions of the GABA B agonist baclofen on a variety of neurons (reviewed by Reisine 1990;Misgeld et al 1995). PT has also been shown to prevent absence seizures induced by GHB, an effect that has been attributed to an increase in a GABA B receptor-mediated K ϩ conductance in thalamocortical neurons (Williams et al 1995). Although it is not yet known whether PT blocks the inhibitory effects of GHB on DA neurons, recent studies have shown that the drug increases a K ϩ conductance in these cells that can be antagonized by CGP-35348 (Madden and Johnson 1998).…”

γ-Aminobutyric acid type B receptors are expressed and functional in mammalian cardiomyocytes

“…Binding assays have cast some doubt on the hypothesis that GHB acts directly through postsynaptic GABA type B (GABA B ) receptors (GABA B Rs) to produce absence seizures (8). However, several reports suggest a direct interaction of GHB with native GABA B Rs; these comprise binding studies (9), as well as electrophysiological studies on dopaminergic (10,11), thalamocortical (12), and hippocampal neurons (13). Moreover, following the cloning of the GABA B receptor that functions as a heterodimer coupling GABA B R1 and GABA B R2 (14 -18), it has been demonstrated that GHB acts like an agonist toward recombinant heterologously expressed GABA B Rs (19).…”

“…Millimolar concentrations of GHB are required to cause dose-dependent hyperpolarizations through the activation of an outward K ϩ conductance that could be inhibited by GABA B receptor antagonists (10)(11)(12)(13)19). In contrast, the GABA B agonist baclofen induces quite similar effects, with an EC 50 of 3-5 M for GABA B R-activated inwardly rectifying K ϩ currents (20,21).…”