Anxiolytic-like effects of 5-HT2 ligands on three mouse models of anxiety.
The behavioural effects of 5-HT(2) receptor agonists, 5-HT(2A) and 5-HT(2C) receptor antagonists were investigated in the mouse four plates test (FPT), light/dark paradigm (L/D) and the elevated plus maze (EPM), in order to elucidate the role of the 5-HT(2) receptor subtypes in these models and to address the inconclusive results previously reported using rat psychopharmacological models. All compounds were administered intraperitoneally 30 min before each test. DOI, a preferential 5-HT(2A) agonist (0.5-8 mg/kg) and BW 723C86, a 5-HT(2B) agonist (8 and 16 mg/kg) provoked an anxiolytic-like response in the FPT. In the EPM, an anxiolytic-like effect was observed for DOI (0.5, 1 and 2 mg/kg), BW 723C86 (0.5, 4, 8 and 16 mg/kg), RO 60-0175 a 5-HT(2C) agonist (4 mg/kg) and the non-selective 5-HT(2) receptor agonist mCPP (0.25 mg/kg.). Ketanserin, a 5-HT(2A/2C) non-selective receptor antagonist (0.015 and 0.03 mg/kg), induced an anxiogenic-like effect in the L/D paradigm. The 5-HT(2C) antagonists (RS 10-2221, SDZ SER082 and SB 206553) were without effect in all three tests. These behavioural results are indicative of an anxiolytic-like action of 5-HT(2) receptor agonists, an anxiogenic-like effect of 5-HT(2A) receptor antagonism, whereas the blockade of 5-HT(2C) receptors are without effect in the mouse models studied.
Nic Dhonnchadha
Bríd Aine
BA
EA 3256 Neurobiologie de l'Anxiété et de la Dépression, Laboratoire Pharmacologie et GIS Medicament, Faculté Médecien et GIS Medicament, BP 53508, 1 rue Gaston Veil, F44035 Nantes, Cedex 01, France.
Bourin
Michel
M
Hascoët
Martine
M
D000662:Amphetamines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009287:Naphthyridines / Q000494:pharmacology / Q000627:therapeutic use; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011930:Reaction Time / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D013141:Spiro Compounds / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000662:Amphetamines; D014151:Anti-Anxiety Agents; D005021:Ethylamines; D007211:Indoles; D009287:Naphthyridines; D010879:Piperazines; D011725:Pyridines; C103848:Ro 60-0175; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D013449:Sulfonamides; D013876:Thiophenes; D000077489:Piperazine; D007650:Ketanserin; C094868:SB 206553; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine