Anxiolytic-like properties of melatonin receptor agonists in mice: involvement of mt1 and/or MT2 receptors in the regulation of emotional responsiveness.
The anxiolytic-like properties of melatonin have been established in rodents. The present study investigated the possible involvement of melatonin receptors/binding sites in the regulation of emotional responsiveness in mice, using an mt1/MT2 receptor specific agonist (S 23478) and two specific ligands of MT3 binding sites with agonistic properties (N-acetylserotonin (NAS) and 5-methoxycarbonylamino N-acetyltryptamine (5-MCA-NAT)). We examined the behavioural effects of these compounds in C3H/He mice confronted with two anxiety models: the free-exploratory test, in which C3H/He mice present neophobic reactions ("trait" anxiety), and the light/dark choice test, which is an unconditioned conflict test (inducing "state" anxiety). Melatonin and S 23478 decreased anxious reactions in both the free-exploratory test (5-25 mg/kg) and the light/dark choice test (melatonin: 20 mg/kg; S 23478: 10-20-40 mg/kg). NAS exerted anxiolytic-like effects only at a dose of 35 mg/kg in the free-exploratory test and at a dose of 40 mg/kg in the light/dark choice test. Finally, 5-MCA-NAT was devoid of anxiolytic-like effects in both tests. These results suggest that the anxiolytic properties of melatonin could involve the activation of mt1 and/or MT2 receptors rather than of the MT3 binding site.
Kopp
C
C
Laboratoire d'Ethologie et de Neurobiologie, 7 rue de l'Université, 67000, Strasbourg, France. kopp@pharma.unizh.ch
Vogel
E
E
Rettori
M
M
Delagrange
P
P
Misslin
R
R
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D000090023:Metallothionein 3; D051379:Mice; D008809:Mice, Inbred C3H; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000502:physiology; D044094:Receptors, Melatonin; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
C413586:5-methoxycarbonylamino-N-acetyltryptamine; D014151:Anti-Anxiety Agents; D006574:Heterocyclic Compounds, 2-Ring; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C413585:S 23478; D014363:Tryptamines; C043464:N-acetyltryptamine; D012701:Serotonin; D008550:Melatonin; C006389:N-acetylserotonin