Castejón A M, Cubeddu L X
Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas.
Pharmacol Biochem Behav. 1998 Dec;61(4):451-7. doi: 10.1016/s0091-3057(98)00131-2.
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.
采用鸽子的操作性冲突任务研究了选择性5-羟色胺3（5-HT3）受体拮抗剂昂丹司琼的抗冲突作用。通过呈现食物刺激行为（啄键）。采用固定间隔程序，交替进行受惩罚（电击）和不受惩罚的反应。在两种惩罚强度水平下评估药物的效果；即，在受惩罚间隔期间的基线反应是未受惩罚反应率的5%（较高惩罚）或10%（较低惩罚）。仅当鸽子处于较低惩罚水平时，昂丹司琼才释放被惩罚抑制的反应。在这些条件下，昂丹司琼（100微克/千克，静脉注射）使啄键次数比对照和赋形剂值增加了119%，并使鸽子在受惩罚间隔期间接受的电击次数增加了一倍。与昂丹司琼类似，丁螺环酮（0.3和1毫克/千克）和地西泮（1和1.5毫克/千克）的抗冲突作用强烈依赖于惩罚刺激的强度。当通过施加更高强度的电击将受惩罚反应抑制到未受惩罚反应的5%时，地西泮和丁螺环酮的抗冲突作用可忽略不计。然而，在较低惩罚水平下，地西泮和丁螺环酮产生的抗冲突作用比昂丹司琼大得多（p<0.001）。这些结果表明，昂丹司琼在释放被惩罚抑制的行为（类抗焦虑作用）方面表现出适度的作用，这高度依赖于所施加的惩罚强度。有人提出，对惩罚的致焦虑反应对5-HT3拮抗剂的敏感性低于厌恶的、未受惩罚情况下诱导的行为，在这种情况下，5-HT3拮抗剂已显示出与苯二氮䓬类相当的疗效。
