5-HT1C RECEPTOR ANTAGONISTS HAVE ANXIOLYTIC-LIKE ACTIONS IN THE RAT SOCIAL-INTERACTION MODEL
5-HT1C RECEPTOR ANTAGONISTS HAVE ANXIOLYTIC-LIKE ACTIONS IN THE RAT SOCIAL-INTERACTION MODEL
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DOI：
10.1007/bf02245165
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发表时间：
1992-06-01
影响因子：
3.4
通讯作者：
KENNETT, GA
中科院分区：
文献类型：
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作者：
KENNETT, GA
一系列5-HT受体拮抗剂的作用在焦虑的动物模型中进行了检查-社会互动测试。6个具有高亲和力的5-HT 1C受体拮抗剂，米安色林，（+）米安色林，1-萘基哌嗪，ICI 169 - 369，pizotifen和LY 53857都增加了时间在积极的社会互动对体重匹配的大鼠在高光陌生的条件下。由于运动仅由I-NP增加，并且仅在高剂量下增加，因此药物的作用与抗焦虑作用一致。苯二氮卓类抗焦虑药利血平（chlordiazepoxide）具有这些特性，但特异性5-HT 2拮抗剂酮色林（ketanserin）和阿坦色林（altanserin）以及5-HT 1A和5-HT 1B拮抗剂氰基吲哚洛尔（cyanopindolol）和吲哚洛尔（pindolol）不具有这些特性。同样，肾上腺素能α-2拮抗剂咪唑克生、α-2拮抗剂和假定的5-HT 1D部分激动剂育亨宾或H1拮抗剂美托咪胺均无任何显著作用。由于（+）米安色林、LY 53857和ICI 169 369至少对5-HT 3受体具有低亲和力，因此这些受体也不可能参与。因此，结果表明，观察到的药物的抗焦虑作用可能是由5-HT 1C受体阻滞剂介导的。
The effects of a range of 5-HT receptor antagonists were examined in an animal model of anxiety - the social interaction test. Six antagonists with high affinity for 5-HT1C receptors; mianserin, (+) mianserin, 1-naphthyl piperazine, ICI 169 369, pizotifen and LY 53857 all increased the time spent in active social interaction by pairs of weight-matched rats under high light unfamiliar conditions. As locomotion was only increased by I-NP and then only at high doses, the effect of the drugs is consistent with anxiolysis. These properties were shared by the benzodiazepine anxiolytic chlordiazepoxide but not by the specific 5-HT2 antagonists ketanserin and altanserin, nor by the 5-HT1A and 5-HT1B antagonists cyanopindolol and pindolol. Similarly, neither the adrenergic-alpha-2 antagonist idazoxan, the alpha-2 antagonist and putative 5-HT1D partial agonist yohimbine nor the H1 antagonist mepyramine had any significant effect. Since (+)mianserin, LY 53857 and ICI 169 369 at least have low affinity for 5-HT3 receptors these receptors are also unlikely to be involved. The results therefore imply that the observed anxiolytic effects of the drugs are likely to be mediated by 5-HT1C receptor blockade.