Preliminary observations on the suppression of nocturnal plasma melatonin levels by short-term administration of diazepam in humans.
Several studies suggest that GABAergic mechanisms may be involved in the modulation of melatonin secretion. However, conflicting results have been reported in animal studies; in humans the issue has not been widely investigated. In the present study, using a double-blind design, six healthy men received orally, at midnight, 10 mg of diazepam, a GABAergic agent, or placebo, on two different occasions 1 week apart. Blood samples were collected, in the dark, immediately before the drug administration, and at 12:30, 1, 2, 3, and 4 AM. Serum melatonin was measured by a radioimmunological method with [125I]melatonin as a tracer. Two-way ANOVA with repeated measurements disclosed a significant effect for treatment (P less than 0.01), for time (P less than 0.0004), and for treatment X time interaction (P less than 0.05). Following diazepam administration, serum melatonin levels observed at 2, 3, and 4 AM were significantly lower than the corresponding values following placebo (P less than 0.002 at 2 and 4 AM; P less than 0.03 at 3 AM [Students' paired t test]). These results show that nocturnal blood melatonin levels may be suppressed by the acute administration of a GABAergic agent, suggesting that GABA may be involved in the modulation of pineal activity in man.
Monteleone
P
P
Institute of Medical Psychology and Psychiatry, First Medical School, University of Naples, Italy.
Forziati
D
D
Orazzo
C
C
Maj
M
M
D000328:Adult; D002940:Circadian Rhythm; D003975:Diazepam / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D008550:Melatonin; D003975:Diazepam