Ohyama Masayo, Kondo Maho, Yamauchi Miki, Imanishi Taiichiro, Koyama Tsukasa
1Pharmaceutical Research Center,Meiji Seika Pharma Co., Ltd.,Kohoku-ku,Yokohama,Japan.
2Ohyachi Hospital,Clinical Research Center,Atsubetsu,Sapporo,Japan.
Acta Neuropsychiatr. 2016 Dec;28(6):327-336. doi: 10.1017/neu.2016.17. Epub 2016 Apr 21.
Asenapine is an atypical antipsychotic that is currently available for the treatment of schizophrenia and bipolar I disorder. Although the atypical antipsychotics clozapine and olanzapine are effective for depression and anxiety in schizophrenia, as demonstrated by animal model studies, this has not been clarified for asenapine. Therefore, we compared the effects of asenapine in the conditioned fear stress model with those of clozapine and olanzapine.
Rats were individually fear conditioned using electrical foot shock in a Skinner box. Approximately 24 h later, individual animals were returned to the same Skinner box (without electrical shock) and their freezing behaviour was observed for 5 min. Animals were treated with asenapine, clozapine, olanzapine, the 5-HT1A receptor partial agonist buspirone, or the 5-HT2C receptor antagonist SB242084 at 30 min before freezing behaviour assessment. The 5-HT1A receptor antagonist WAY100635 or the 5-HT2C receptor agonist Ro60-0175 was also used concomitantly with asenapine. The effects of asenapine, clozapine, and olanzapine on serotonin release in the rat hippocampus were also measured using in vivo microdialysis.
Asenapine reduced freezing behaviour, while neither clozapine nor olanzapine reduced freezing behaviour. Buspirone and SB242084 also reduced freezing behaviour. The effect of asenapine in reducing freezing behaviour was not altered by the concomitant administration of WAY100635 or Ro60-0175. Both asenapine and clozapine, but not olanzapine, increased serotonin release in the rat hippocampus.
Asenapine may have superior therapeutic effect on anxiety symptoms than other agents, although the underlying mechanism of its anxiolytic activity remains unknown.
阿塞那平是一种非典型抗精神病药物，目前可用于治疗精神分裂症和双相I型障碍。尽管动物模型研究表明，非典型抗精神病药物氯氮平和奥氮平对精神分裂症中的抑郁和焦虑有效，但阿塞那平的这一作用尚未明确。因此，我们在条件性恐惧应激模型中比较了阿塞那平与氯氮平和奥氮平的效果。
在斯金纳箱中使用电足部电击对大鼠进行个体恐惧条件训练。约24小时后，将个体动物放回同一斯金纳箱（无电击），观察其僵住行为5分钟。在僵住行为评估前30分钟，用阿塞那平、氯氮平、奥氮平、5-HT1A受体部分激动剂丁螺环酮或5-HT2C受体拮抗剂SB242084对动物进行治疗。5-HT1A受体拮抗剂WAY100635或5-HT2C受体激动剂Ro60-0175也与阿塞那平联合使用。还使用体内微透析法测量阿塞那平、氯氮平和奥氮平对大鼠海马中5-羟色胺释放的影响。
阿塞那平可减少僵住行为，而氯氮平和奥氮平均未减少僵住行为。丁螺环酮和SB242084也可减少僵住行为。同时给予WAY100便或Ro60-0175不会改变阿塞那平减少僵住行为的效果。阿塞那平和氯氮平均可增加大鼠海马中的5-羟色胺释放，而奥氮平则无此作用。
尽管阿塞那平抗焦虑活性的潜在机制尚不清楚，但它对焦虑症状可能具有比其他药物更优的治疗效果。
