Anxiolytic-like profile of p-MPPI, a novel 5HT1A receptor antagonist, in the murine elevated plus-maze.
Recent research on the effects of selective 5-HT1A receptor antagonists in animal models of anxiety has yielded inconsistent findings. In the present study, the behavioural effects of the novel 5-HT1A receptor antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl) -p-iodobenzamido]-ethyl-piperazine (p-MPPI), were examined in male mice using an ethological version of the elevated plus-maze test. Results show that at lower doses (0.5-4.5 mg/kg), p-MPPI produced a significant and dose-related anxiolytic profile on both conventional (open arm avoidance) and ethological (risk assessment) measures. However, these effects were lost at a higher dose (13.5 mg/kg) which, instead, increased grooming and immobility. The behavioural profile of p-MPPI is contrasted with those previously obtained with other 5-HT1A receptor ligands (agonists, partial agonists and antagonists), and it is suggested that 5-HT1A receptor antagonists may possess therapeutic advantages in anxiety disorders.
Cao
B J
BJ
Department of Psychology, University of Leeds, UK.
Rodgers
R J
RJ
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000631:Aminopyridines; D010879:Piperazines; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine