Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
J Psychopharmacol. 2010 Jul;24(7):1045-53. doi: 10.1177/0269881109102546. Epub 2009 Mar 27.
Antipsychotic drugs selectively suppress conditioned avoidance response. Using a two-way active avoidance response paradigm, we examined the role of drug-induced interoceptive state in the mediation of avoidance-suppressive effect. In Experiment 1, we found that rats intermittently treated with olanzapine (OLZ) (1.0 mg/kg, s.c.) or haloperidol (0.03 mg/kg, s.c.) on the 1st day of a 3-day cycle for seven cycles exhibited a progressive across-session decline in avoidance responding, despite the fact that they exhibited a comparable high level of avoidance responding on the 3rd day of each cycle during the drug-free retraining session. In Experiments 2 and 3, rats that were previously treated with OLZ (0.5-2.0 mg/kg, s.c.) or risperidone (0.2-1.0 mg/kg) during the acquisition phase of avoidance conditioning exhibited significantly fewer avoidance responses when they were retested 3 weeks later to the same drug in comparison to rats that were previously treated with nonantipsychotic drugs (chlordiazepoxide, 10 mg/kg, citalopram 10 mg/kg, or sterile water). Overall, these findings indicate a 'drug memory'-like mechanism that maintains the avoidance-suppressing effect of antipsychotics over time. This mechanism is likely driven by the interoceptive state caused by the antipsychotics, which may also be an important behavioral mechanism mediating the clinical effects of antipsychotic treatments.
抗精神病药物选择性地抑制条件性回避反应。使用双向主动回避反应范式,我们研究了药物引起的内感受状态在介导回避抑制效应中的作用。在实验 1 中,我们发现,在 7 个周期的 3 天周期中,每隔一天用奥氮平(OLZ)(1.0mg/kg,sc)或氟哌啶醇(0.03mg/kg,sc)间歇性治疗的大鼠,尽管在无药物重新训练期间,它们在每个周期的第 3 天表现出相当高的回避反应,但在整个疗程中表现出跨疗程回避反应逐渐下降。在实验 2 和 3 中,先前在回避条件反射获得阶段用 OLZ(0.5-2.0mg/kg,sc)或利培酮(0.2-1.0mg/kg)治疗的大鼠,当在 3 周后用相同药物重新测试时,回避反应明显少于以前用非抗精神病药物(地西泮,10mg/kg,西酞普兰 10mg/kg 或无菌水)治疗的大鼠。总体而言,这些发现表明存在一种“药物记忆”样机制,可随着时间的推移维持抗精神病药物的回避抑制作用。这种机制可能是由抗精神病药物引起的内感受状态驱动的,这也可能是介导抗精神病药物治疗临床效果的重要行为机制。