Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze
Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze
复制标题
DOI：
10.1007/s00213-005-0108-2
复制
发表时间：
2005-11-01
影响因子：
3.4
通讯作者：
Landeira-Fernandez, J
中科院分区：
文献类型：
--
作者：
Cruz, APM;Pinheiro, G;Landeira-Fernandez, J
基本原理：虽然5-HT 2受体似乎在焦虑中起着重要作用，但许多研究的结果仍然存在很大差异。目的：本研究旨在：（1）进一步探讨高架十字迷宫（elevated plus-maze，EMAW）和开放式竞技场（open-field arena）两种广泛应用于研究焦虑和运动活动的动物模型对5-HT（2）受体激活的影响;方法：实验一：雄性Wistar大鼠腹腔注射（i. p.）(1.0 ml/kg）注射1.0、2.0或4.0 mg/kg剂量的优选5-HT 2C受体激动剂6-氯-2 [1-哌嗪基]吡嗪（MK-212）。对照组动物注射生理盐水。采用开放臂条目的百分比和在这些臂中花费的时间的百分比作为焦虑指数，而闭合臂条目的数量被计算为自发活动的指示。在第二项实验中，将大鼠暴露于旷场竞技场中10 min，以进一步评估相同MK-212剂量对自发活动的干扰。在实验3中，在腹膜内注射生理盐水或中等剂量MK-212（2.0 mg/kg）后12 min，将混合5-HT 2A/2C受体拮抗剂利坦色林（0.5、1.25、2.5和5.0 μ g）或其溶媒显微注射（0.2 μ l）到大鼠BLA中。结果：MK-212最高剂量（4.0 mg/kg）可引起运动抑制，但中剂量（2.0 mg/kg）可减少开臂探索次数，对闭臂进入次数无显著影响。这种行为特征，与选择性焦虑的影响，在海马，剂量依赖性地防止利坦色林微量输注到BLA。然而，在盐水预处理的动物，利坦色林（所有剂量）是无效的。结论：MK-212增加焦虑和减少自发活动。通过阻断BLA内的5-HT 2受体来防止5-HT 2受体激活的致焦虑样特征，其本身对由BLA触发的基础焦虑水平没有影响。
Rationale: Although 5-HT2 receptors seem to play an important role in anxiety, results from numerous studies are still highly variable. Moreover, little is known about the behavioral effects of centrally administered 5HT(2) compounds in animal models of anxiety.Objective: The current study was performed to: (1) further investigate the effects of 5-HT2 receptor activation in rats exposed to the elevated plus-maze (EPM) and the open-field arena, two widely used animal models for studying anxiety and locomotor activity; and (2) evaluate the involvement of the 5-HT2 receptors within the basolateral nucleus of the amygdala (BLA) in the modulation of such effects.Methods: In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT2C receptor agonist 6-chloro-2 [1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg. Control animals were injected with saline. The percentage of open-arm entries and the percentage of time spent in these arms were employed as anxiety indexes, whereas the number of closed-arm entries was calculated as indicative of locomotor activity. In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity. In Experiment 3, rats were microinjected (0.2 mu l) either with the mixed 5-HT2A/2C receptor antagonist ritanserin (0.5, 1.25, 2.5, and 5.0 mu g) or its vehicle into the BLA 12 min following i.p. injections of saline or the intermediate dose of MK-212 (2.0 mg/kg). Fifteen minutes later, each animal was exposed to the EPM as before.Results: Whereas the highest dose of MK-212 (4.0 mg/kg) induced motor-suppressant effects in both EPM and open-field arena, the intermediate dose of the drug (2.0 mg/kg) reduced open-arm exploration without significantly affecting the number of closed-arm entries. This behavioral profile, consistent with selective anxiogenic effect in the EPM, was dose-dependently prevented by ritanserin microinfusion into the BLA. In saline-pretreated animals, however, ritanserin (all doses) was ineffective.Conclusions: MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT2 receptor activation is prevented by the blockade of 5-HT2 receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM.