Gamma-hydroxybutyric acid as a signaling molecule in brain

Gamma-hydroxybutyric acid was synthesized 35 years ago to obtain a GABAergi c substance that penetrates the brain freely. Since then, gamma-hydroxpbuty ric acid has been used in human beings for its sedative and anesthetic prop erties when administered at high doses, and most of the studies on gamma-hy droxybutyric acid have focused on its pharmacological effects. However, gam ma-hydroxybutyric acid is also an endogenous substance, which is synthesize d and released in thr brain by specific neuronal pathways, implicated in th e control of the GABAergic, dopaminergic, and opioid systems. This control is mediated by specific gamma-hydroxybutyric acid receptors with a unique d istribution in brain and a specific ontogenesis and pharmacology. Stimulati on of these recrptors induces specific cellular responses. Taken together, these results suggest that gamma-hydroxybutyric acid possesses most of the properties required of a neurotransmitter/neuromodulator in the brain. (C) 2000 Elsevier Science Inc. All rights reserved.