Level of punishment determines anticonflict activity of ondansetron in pigeons: comparison with buspirone and diazepam.

The anticonflict effect of the selective 5-HT3 receptor antagonist, ondansetron, was investigated employing an operant conflict task in pigeons. Behavior (key pecking) was stimulated by food presentation. A fixed-interval program of alternated punished (electrical shocks) and unpunished responding was employed. The effects of drugs were evaluated at two levels punishment intensity; i.e., baseline responding during the punished interval was 5% (higher punishment) or 10% (lower punishment) of the unpunished responding rate. Ondansetron released responding suppressed by punishment only when pigeons were working at the lower levels of punishment. Under these conditions, ondansetron (100 microg/kg, i.v.), increased key pecking by 119% above control and vehicle values, and doubled the number of shocks received by the pigeons during the punished intervals. Similarly to ondansetron, the anticonflict effects of buspirone (0.3 and 1 mg/kg) and diazepam (1 and 1.5 mg/kg) were strongly dependent on the intensity of the punishing stimulus. When punished responding was suppressed to 5% of unpunished responding by applying shocks of higher intensity, diazepam and buspirone had negligible anticonflict action. However, at lower levels of punishment, diazepam and buspirone produced much greater anticonflict effects than ondansetron (p < 0.001). These results indicate that ondansetron exhibits a modest effect in releasing behaviors suppressed by punishment (anxiolytic-like action), which was highly dependent on the intensity of punishment applied. It is proposed that the anxiogenic response to punishment is less sensitive to 5-HT3 antagonists than the behavior induced by aversive, unpunished situations, where 5-HT3 antagonists have shown comparable efficacy to benzodiazepines.