Anxiolytic-like profile of p-MPPI, a novel 5HT(1A) 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.