Effects of Sodium Valproate and Diazepam on Beta-Endorphin, Beta-Lipotropin and Cortisol Secretion Induced by Hypoglycemic Stress in Humans

Abstract

Evidence that γ-aminobutyric acid (GABA) and benzodiazepine receptors play a role in the inhibition of ACTH-cortisol secretion in humans has until now been drawn only from data indicating that sodium valproate, a GABA mimetic, and diazepam, a benzodiazepine, decrease hypothalamus-pituitary-adrenal (HPA) axis secretion in patients affected by pathological hypersecretion of the axis. Therefore, the present study investigated the effects, in the same healthy subjects, of sodium valproate or diazepam, on both basal and stress-stimulated concentrations of β-endorphin (β-EP), β-lipotropin (β-LPH) and cortisol. A single maximal dose of sodium valproate (400 mg) or diazepam (10 mg) did not significantly modify basal concentrations of β-EP, β-LPH and cortisol. On the other hand, in the same subjects, pretreatment with sodium valproate (20 mg × 3) or diazepam (10 mg × 2) blocked the increases in these hormones produced by hypoglycemic stress in all patients tested (p< 0.01 vs. placebo at 45, 60 and 90 min after insulin injection), without affecting the decrease in blood glucose levels. The present data show that sodium valproate and diazepam inhibit stress-induced β-EP, β-LPH and cortisol secretion in humans, suggesting that endogenous GABA and benzodiazepine receptors participate in physiological mechanisms regulating the activity of the HPA axis.