Anxiolytic-like properties of melatonin receptor agonists in mice: involvement of mt1 and/or MT2 receptors in the regulation of emotional responsiveness

Neuropharmacology. 2000 Jul 24;39(10):1865-71. doi: 10.1016/s0028-3908(99)00263-4.

Abstract

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.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Heterocyclic Compounds, 2-Ring / pharmacology
  • Male
  • Melatonin / pharmacology
  • Metallothionein 3
  • Mice
  • Mice, Inbred C3H
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / physiology
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Melatonin
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Tryptamines / pharmacology

Substances

  • 5-methoxycarbonylamino-N-acetyltryptamine
  • Anti-Anxiety Agents
  • Heterocyclic Compounds, 2-Ring
  • Metallothionein 3
  • Mt3 protein, mouse
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • S 23478
  • Tryptamines
  • N-acetyltryptamine
  • Serotonin
  • Melatonin
  • N-acetylserotonin