FLUMAZENIL EFFECTS ON GROWTH-HORMONE RESPONSE TO GAMMA-HYDROXYBUTYRICACID

Gamma-hydroxybutyric acid (GHBA) has been recently introduced for alco hol detoxication but few data are available concerning the central mec hanism of action of this gamma-aminobutyric acid (GABA) catabolite. GH BA ability to stimulate growth hormone (GH) and prolactin (PRL) secret ion has been reported: the involvement of GABA, dopamine or serotonin systems acting on pituitary hormones has been hypothesized. In the pre sent study we investigated GH and PRL responses to GHBA with or withou t flumazenil (a benzodiazepine receptor antagonist) i.v. pretreatment. Our study included nine male healthy volunteers (aged 23.2 +/- 2.5 ye ars) who were submitted to three tests in random order: (1) oral GHB a dministration; (2) oral GHBA and i.v. flumazenil administration; (3) o ral placebo and i.v. saline administration. Blood samples for GH and P RL 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 leve ls; flumazenil pretreatment antagonized GHBA action on GH secretion. N o changes were obtained with placebo and saline administration. A subp opulation of GABA receptors or GHBA-specific receptors seems to be inv olved in GHBA action. The benzodiazepine receptor antagonist flumazeni l was able to influence the sensitivity and the neuroendocrine consequ ences of GHBA binding site stimulation.