ABSTRACT
Originally, γ-hydroxybutyrate (GHB) was synthesized about forty years ago in the hope of obtaining a GABA-like substance, able to pass freely through the blood brain barrier (Laborit 1964). In initial studies, the pharmacological properties of this compound seemed to mimic a general GABAergic effect, despite the fact that an enormous amount of exogenous GHB (several grams) was necessary to induce sedation or anesthesia in humans (Laborit 1973). Later on, the physiological presence of micromolar concentrations of GHB in the brain of several mammalian species was demonstrated (Roth and Giarman 1970). The problem of the functional role of GHB was not addressed at first because interest was mainly focused on its pharmacological and therapeutic use. Until recently, the mechanisms supporting these effects were poorly understood but data have now been accumulated that favor a neuromodulator/neuroregulator role for endogenous GHB (Vayer et al. 1987b). Modifications of the plasticity of this system by massive exogenous administration of GHB have shed some light on the molecular pharmacology of these neuromodulatory pathways.
