Anxiolytic-like effects observed in rats exposed to the elevated zero-maze following treatment with 5-HT2/5-HT3/5-HT4 ligands.
The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT2C antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT2C agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT3 antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT3 agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg), and in the third experiment, we administered the 5-HT4 antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT4 agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT2/3/4 subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT2 and 5-HT3 agonists, the 5-HT4 agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT4 antagonist RS 39604. We conclude by discussing the implications of these findings.
School of Psychology, Queen's University, Belfast, Northern Ireland, UK.
Rob
R
Bell
1] Department of Psychology, University of Kentucky, USA [2] Department of Psychology, Grenoble-Alpes University, France.
Aaron A
AA
Duke
School of Psychology, Queen's University, Belfast, Northern Ireland, UK.
Paula E
PE
Gilmore
School of Psychology, Queen's University, Belfast, Northern Ireland, UK.
Deaglan
D
Page
Department of Psychology, Grenoble-Alpes University, France.
Laurent
L
Bègue
D000814:Aniline Compounds / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D003975:Diazepam / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010078:Oxazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011407:Propane / Q000031:analogs & derivatives / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D013141:Spiro Compounds / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000814:Aniline Compounds; D014151:Anti-Anxiety Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010078:Oxazines; D010880:Piperidines; D011719:Pyrazines; C475107:RS 39604; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D013449:Sulfonamides; C107826:RS 67333; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C070671:azasetron; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride; D003975:Diazepam; D011407:Propane