Effect of GABAergic ligands on the anxiolytic-like activity of DOI (a 5-HT(2A/2C) agonist) in the four-plate test in mice.
5-HTergic and GABAergic systems are involved in neurobiology of anxiety. Precedent studies have demonstrated that SSRIs possessed an anxiolytic-like effect in the four-plate test (FPT) at doses that did not modify spontaneous locomotor activity. This effect seems to be mediated through the activation of 5-HT(2A) postsynaptic receptors. The purpose of the present study was to examine the implication of GABA system in the anxiolytic-like activity of DOI in the FPT. To achieve this, the co-administration of DOI (5-HT(2A/2C) receptor agonists) with GABA(A) and GABA(B) receptor ligands was evaluated in the FPT. Alprazolam, diazepam and muscimol (for higher dose) potentiated the anxiolytic-like effect of DOI. Bicuculline, picrotoxin and baclofen inhibited the anxiolytic-like effect of DOI. Flumazenil and CGP 35348 had no effect on the anxiolytic-like activity of DOI. These results suggest that the GABA system seems to be strongly implicated in the anxiolytic-like activity of DOI in the FPT.
Massé
Fabienne
F
EA 3256 "Neurobiologie de l'Anxiété et de la Dépression", Faculté de Médecine, BP 53508, 1 rue Gaston Veil, F44035 Nantes cedex 01, France.
Hascoët
Martine
M
Bourin
Michel
M
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D014151:Anti-Anxiety Agents; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; D005442:Flumazenil; C066430:CGP 35348; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D001640:Bicuculline