High affinity binding site for γ-hydroxybutyric acid in rat brain

Cataleptic effects of γ-hydroxybutyrate (GHB) and baclofen in mice: mediation by GABAB receptors, but differential enhancement by N-methyl-d-aspartate (NMDA) receptor antagonists

“…GHB binds to GABA B receptors (Mathivet et al 1997;Lingenhoehl et al 1999) and specific GHB receptors (Benavides et al 1982;Snead and Liu 1984) in brain that are thought to be involved in the behavioral effects of GHB. At present, there appears to be little evidence for a role for GHB receptors in the in vivo effects of GHB (Wong et al 2004).…”

α4βδ GABA A receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)

“…Additionally, GHB is a drug of abuse (Fantasy) and a registered drug for treating narcolepsy (2) and alcoholism (3). GHB binds to at least two distinct populations of low-and high-affinity binding sites in the brain (4). When GHB is ingested in high doses and reaches millimolar concentrations in the brain, it induces behavioral effects such as sedation, motor incoordination and hypothermia (3).…”

“…These actions are largely mediated by metabotropic GABA B receptors, because effects are prevented by GABA B receptor antagonist pretreatment (5) and completely abolished in GABA B(1) KO mice (6). In addition to the validated GABA B receptor effects and other suggested receptors (7), GHB binds with nanomolar to micromolar affinity to a remarkably abundant protein of distinct spatial distribution and ontogenesis (4), representing an additional functional target. Interestingly, this high-affinity binding protein is preserved in GABA B(1) KO mice (6) and can be specifically probed with BnOPh-GHB) (8).…”

Gamma-hydroxybutyrate Reduces GABAA-mediated Inhibitory Postsynaptic Potentials in the CA1 Region of Hippocampus

“…In fact, synthesis, release, uptake mechanisms, and specific binding sites for GHB have been identified in the mammalian brain (Benavides et al 1982a,b;Hechler et al 1985Hechler et al , 1992Maitre et al 1983;Rumigny et al 1981;Snead and Liu 1984;Vayer et al 1988). GHB binding sites exhibit high and low (about 20 M) affinity for GHB (Benavides et al 1982a) and are sensitive to pertussis toxin, suggesting that these sites could represent G protein coupled receptors (Kemmel et al 1998;Rotomponirina et al 1995). GHB binding sites have a discrete brain distribution including the frontal cortex, nucleus accumbens, amygdala, hypothalamus, and, with highest density, the hippocampus (Hechler et al 1992;Maitre et al 2000;Snead et al 1990).…”