Profile of action of 5-HT3 receptor antagonists, ondansetron and WAY 100289, in the elevated plus-maze test of anxiety of mice.
The effects of ondansetron (0.001-0.1 mg/kg) and the novel 5-HT3 receptor antagonist, WAY 100289 (0.01-10.0 mg/kg), on anxiety were examined in male mice using an ethological version of the elevated plus-maze paradigm. This procedure involves scoring specific aspects of defensive behaviour in addition to the more usual spatiotemporal measures. Results show that, at the doses tested, neither compound produced a behavioural profile consistent with anxiety reduction. Indeed, the lowest dose of ondansetron (0.001 mg/kg) produced some behavioural trends more typically associated with mild anxiety enhancement. Data are discussed in relation to the enigmatic effects of 5-HT3 receptor antagonists in animal models of anxiety. It is suggested that the large within- and between-test variability observed with these compounds may indicate an action on mechanisms other than anxiety.
Rodgers
R J
RJ
Department of Psychology, University of Leeds, UK.
Cole
J C
JC
Tredwell
J M
JM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D017294:Ondansetron / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C077614:WAY 100289; D017294:Ondansetron