Melatonin as an anxiolytic in rats: time dependence and interaction with the central GABAergic system.
Anxiolytic and pro-exploratory melatonin properties were assessed in rats using a plus-maze procedure. Both melatonin (1 mg/kg) and diazepam (0.5 mg/kg) showed a significant diurnal variation to decrease anxiety and to promote exploratory behavior. Melatonin displayed anxiolytic activity at night, with absence of effects at noon and a weak activity at the beginning of the light phase. Melatonin pro-exploratory activity was found only at night. Diazepam exerted significant anxiolysis during the night, with less activity during the day. Diazepam pro-exploratory activity was found during the night only. A dose-response study carried out by injecting 1-20 mg/kg melatonin at 12:00 or 18:00 h indicated that melatonin activity was greatest at 18:00 h. Diazepam was anxiolytic at both times, and pro-exploratory at 18:00 h only. Melatonin activity was blunted by administration of the benzodiazepine antagonist, flumazenil.
Golombek
D A
DA
Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Martini
M
M
Cardinali
D P
DP
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002940:Circadian Rhythm; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D008550:Melatonin; D003975:Diazepam