Repeated administration of 5‐hydroxytryptamine 2C agonist MK212 produces a sensitization effect of antipsychotic activity
Repeated administration of 5‐hydroxytryptamine 2C agonist MK212 produces a sensitization effect of antipsychotic activity
复制标题
DOI：
10.1002/iub.1580
复制
发表时间：
2016-10
期刊：
影响因子：
4.6
通讯作者：
Weihai Chen;Xiaqing Wang;Minmin Yan;Yan Wang;Shixue Xie;Hong Li;Ming Li
中科院分区：
文献类型：
--
作者：
Weihai Chen;Xiaqing Wang;Minmin Yan;Yan Wang;Shixue Xie;Hong Li;Ming Li
在抗精神病药物的几项急性临床前试验中，5-羟色胺2C（5-HT 2C）受体激动剂被认为具有抗精神病活性，锥体外系副作用可能性较低。然而，对长期使用5-HT 2C受体激动剂的长期影响知之甚少。本研究检查了在条件性回避反应和MK 801诱导的过度运动试验中，用高选择性5-HT 2C受体激动剂MK 212重复激活5-HT 2C受体是否会诱导其抗精神病样活性的长期变化（致敏或耐受）。Sprague-道利大鼠首先在腹膜内（i. p.）MK212（0.25、0.5、1.0 mg/kg）处理连续5天。三天后，当所有大鼠注射低剂量MK 212（0.25 mg/kg）并检测回避反应时，用1.0和0.5 mg/kg MK 212预处理的大鼠的回避反应显著低于用溶媒（0.9%盐水）处理的大鼠。然而，在MK 801诱导的过度运动试验中，既往药物暴露诱导的组间差异不显著。总体而言，本研究的结果表明，MK212重复给药能够诱导条件性回避反应中抗精神病活性的剂量依赖性致敏。MK212在CAR和MK 801诱导的过度运动中的致敏性差异可能与MK212在这两种试验中的作用机制不同有关。© 2016 IUBMB Life，68（12）：985-993，2016
5‐Hydroxytryptamine 2C (5‐HT2C) receptor agonists have been suggested to possess an antipsychotic activity in several acute preclinical tests of antipsychotic drugs with low extra‐pyramidal side effect liability. However, little is known about the long‐term effect associated with chronic use of 5‐HT2C receptor agonists. The present study examined whether repeated activation of 5‐HT2C receptor with a highly selective 5‐HT2C receptor agonist MK212 would induce a long‐term change in its antipsychotic‐like activity (either a sensitization or tolerance) in the conditioned avoidance response and MK801‐induced hyperlocomotion tests. Sprague‐Dawley rats were first tested under the intraperitoneal (i.p.) treatment of MK212 (0.25, 0.5, 1.0 mg/kg) for 5 consecutive days. Three days later, when all rats were injected with a low dose of MK 212 (0.25 mg/kg) and tested for avoidance responding, rats that had been pretreated with 1.0 and 0.5 mg/kg MK212 made significantly fewer avoidance responses than those that had been treated with vehicle (0.9% saline). However, this past drug exposure‐induced group difference was not significant in the MK801‐induced hyperlocomotion test. Overall, results from this study suggest that repeated treatment of MK212 is capable of inducing a dose‐dependent sensitization of antipsychotic activity in conditioned avoidance response. The discrepancy in sensitization of MK212 in CAR and MK801‐induce hyperlocomotion may be related to the different mechanism underlying the effect of MK212 in these two tests. © 2016 IUBMB Life, 68(12):985–993, 2016