Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid

Gamma-hydroxybutyric acid (GHBA) has been recently introduced for alcohol detoxication but few data are available concerning the central mechanism of action of this gamma-aminobutyric acid (GABA) catabolite. GHBA ability to stimulate growth hormone (GH) and prolactin (PRL) secretion has been reported: the involvement of GABA, dopamine or serotonin systems acting on pituitary hormones has been hypothesized. In the present study we investigated GH and PRL responses to GHBA with or without flumazenil (a benzodiazepine receptor antagonist) i.v. pretreatment. Our study included nine male healthy volunteers (aged 23.2 +/- 2.5 years) who were submitted to three tests in random order: (1) oral GHB administration; (2) oral GHBA and i.v. flumazenil administration; (3) oral placebo and i.v. saline administration. Blood samples for GH and PRL assays were collected during the three tests at -15, 0, 15, 30, 45, 60 and 90 min. GHBA induced a significant increase in GH plasma levels; flumazenil pretreatment antagonized GHBA action on GH secretion. No changes were obtained with placebo and saline administration. A subpopulation of GABA receptors or GHBA-specific receptors seems to be involved in GHBA action. The benzodiazepine receptor antagonist flumazenil was able to influence the sensitivity and the neuroendocrine consequences of GHBA binding site stimulation.