Suppression of nocturnal plasma melatonin levels by evening administration of sodium valproate in healthy humans

To investigate the role of gamma-aminobutyric acid (GABA) in the modulation of human melatonin production, we studied the effects of the acute administration of the GABAergic drug, sodium valproate (VAL), on nocturnal blood melatonin levels in healthy subjects. To this purpose, 4 healthy men and 3 healthy women, aged 24-33 years, underwent three experimental sessions in which they received orally 400 mg VAL, 800 mg VAL, or placebo, in random order, according to a double-blind design. The drug administration was done at 19:00 hours; thereafter blood samples were collected over the night, in dark conditions with the help of a red light. As compared to placebo, VAL, at the dosage of both 400 and 800 mg, significantly suppressed nocturnal blood melatonin levels, the higher dose being slightly more effective than the lower one. The maximum suppression coincided with the highest plasma levels of valproic acid. These findings support the view that endogenous GABA may participate in the modulation of the activity of the human pineal gland. (C) 1997 Society of Biological Psychiatry.