Effect of serotonergic drugs on footshock‐induced ultrasonic vocalization in adult male rats
Effect of serotonergic drugs on footshock‐induced ultrasonic vocalization in adult male rats
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血清素药物对成年雄性大鼠足部电击超声发声的影响
DOI：
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发表时间：
1993
影响因子：
1.6
通讯作者：
Connie Sánchez
中科院分区：
文献类型：
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作者：
Connie Sánchez
成年大鼠在应激条件下（如不可避免的足部电击）发出的超声波发声（20-30 kHz）的调制已被评估为焦虑模型。研究了具有不同内在活性的5-HT 1A受体激动剂的作用，以及其他5-HT 1受体亚型、5-HT 2和5-HT 3受体在超声发声介导中的作用，以及通过给予5-HT抑制剂芬氟拉明或5-HT前体1-5-HTP增加多巴胺能活性的作用。记录4次不可避免的（1.0 mA）足电击后1-6 min发声所用的时间。对5-HT 1A受体具有亲和力的药物（即8-OHDPAT，flesinoxan，ipsapirone，丁螺环酮，吉哌隆，NAN-190）无论其疗效如何，都能消除发声。混合5-HT、受体和β-肾上腺素受体拮抗剂（-）-阿普洛尔和吲哚洛尔抑制足电击诱导的超声发声，而（-）-喷丁洛尔无效。β_1受体拮抗剂美托洛尔和β_2受体拮抗剂ICI 118.551均无效。这表明（-）-烯丙洛尔和吲哚洛尔在测试模型中充当部分5-HT 1激动剂。非选择性5-HT 1受体激动剂eltoprazine、m-CPP和5-MeODMT以及5-HT 2受体激动剂DOI和d-LSD也消除了发声，而5-HT 2受体拮抗剂ritanserin和5-HT 3受体拮抗剂昂丹司琼、ICS 205-930和扎考必利则无作用。（-）-戊丁洛尔逆转8-OHDPAT诱导的抑制。利坦色林逆转DOI诱导的超声发声抑制，但不逆转8-OHDPAT诱导的抑制。这表明在该模型中5-HT 1A和5-HT 2受体之间没有功能性相互作用。芬氟拉明和1-5-HTP剂量依赖性地抑制足电击诱导的超声发声。这些发现表明，该效应最有可能是由突触后5-HT受体介导的，尽管不能排除突触前5-HT受体的贡献。本研究提示5-HT 1A受体和5-HT 2受体参与了超声发声的介导过程。
Modulation of ultrasonic vocalization (20–30 kHz) emitted by adult rats under stressful conditions such as unavoidable foot- shock has been evaluated as a model of anxiety. The effects of 5-HT1A receptor agonists with different intrinsic activities and the role of other 5-HT1 receptor subtypes, and of 5-HT2 and 5-HT3 receptors, in mediation of ultrasonic vocalization were studied, as were the effects of increasing serotonergic activity by administration of the 5-HT releaser fenfluramine or the 5-HT precursor 1–5-HTP. The time spent vocalizing 1–6 min after four inescapable (1.0 mA) footshocks was recorded. Drugs with affinity for 5-HT1A receptors (i.e. 8-OHDPAT, flesinoxan, ipsapirone, buspirone, gepirone, NAN-190) abolished the vocalization irrespective of their efficacy. The mixed 5-HT, receptor and β-adrenoceptor antagonists (-)-alprenolol and pindolol inhibited foot-shock-induced ultrasonic vocalization, whereas (-)-penbutolol was ineffective. The β1-adrenoceptor antagonist metoprolol and the β2-adrenoceptor antagonist ICI 118.551 were without effect. This suggests that (-)-alprenolol and pindolol act as partial 5-HT1 agonists in the test model. The non-selective 5-HT1 receptor agonists eltoprazine, m-CPP and 5-MeODMT and the 5-HT2 receptor agonists DOI and d-LSD also abolished the vocalization, whereas the 5-HT2 receptor antagonist ritanserin and the 5-HT3 receptor antagonists ondansetron, ICS 205–930 and zacopride were without effect. (-)-Penbutolol reversed 8-OHDPAT-induced inhibition. Ritanserin reversed DOI-induced inhibition of ultrasonic vocalization, but not 8-OHDPAT-induced inhibition. This suggests that there is no functional interaction between 5-HT1A and 5-HT2 receptors in this model. Fenfluramine and 1–5-HTP dose-dependently inhibited footshock-induced ultrasonic vocalization. These findings indicate that the effect most likely is mediated by postsynaptic 5-HT receptors, although contribution by presynaptic 5-HT receptors cannot be excluded. In conclusion, this study indicates that 5-HT1A receptors and 5-HT2 receptors are involved in mediation of ultrasonic vocalization.