Biphasic effects of 5-HT1A agonism on impulsive responding are dissociable from effects on anxiety in the variable consecutive number task
Biphasic effects of 5-HT1A agonism on impulsive responding are dissociable from effects on anxiety in the variable consecutive number task
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DOI：
10.1007/s00210-019-01684-5
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发表时间：
2019-11-01
影响因子：
3.6
通讯作者：
McLaughlin, Peter J.
中科院分区：
文献类型：
--
作者：
Groft, Miranda L.;Normann, Marigny C.;McLaughlin, Peter J.
已知血清素能 5-HT1A 受体与冲动和焦虑相关行为有关。尽管焦虑和冲动是不同的概念，但研究表明，焦虑的产生会导致冲动。因此，确定 5-HT1A 受体是否参与冲动行为（独立于其对焦虑的影响）非常重要。 5-HT1A 激动剂 8-OH-DPAT（0.0125-0.1 mg/kg 皮下注射）在低剂量时增加脉冲作用，但在高剂量时减少脉冲作用，在新颖的节奏可变连续数与判别刺激任务 (VCN) 上。 5-HT1A 拮抗剂 WAY 100,635（0.2-1.2 mg/kg 皮下注射）和去甲肾上腺素能拮抗剂和药理应激剂育亨宾（1-2 mg/kg 腹膜内注射）均不会改变冲动性的测量。育亨宾引起的压力足以在高架零迷宫中产生类似焦虑的行为，这证实了 VCN 任务是对不受焦虑影响的冲动行为的选择性测定。我们假设 8-OH-DPAT 的双相效应是由于对突触前中缝 5-HT1A 自受体以及突触后 5-HT1A 受体的作用所致。这些结果表明，这种受体介导冲动行为，并且这并不是其在焦虑中的作用的次要因素。
The serotonergic 5-HT1A receptor is known to be involved in both impulsivity and anxiety-related behavior. Although anxiety and impulsivity are different constructs, it has been shown that anxiogenesis can result in impulsiveness. It is therefore important to determine if the 5-HT1A receptor is involved in the commission of impulsive actions independent of its effects on anxiety. The 5-HT1A agonist 8-OH-DPAT (0.0125-0.1 mg/kg subcutaneous) increased impulsive action at low doses, but decreased it at higher doses, on the novel paced variable consecutive number with discriminative stimulus task (VCN). Neither the 5-HT1A antagonist WAY 100,635 (0.2-1.2 mg/kg subcutaneous), nor the noradrenergic antagonist and pharmacological stressor yohimbine (1-2 mg/kg intraperitoneal) altered measures of impulsivity. Stress induced by yohimbine was sufficient to produce anxiety-like behavior in the elevated zero maze, confirming that the VCN task is a selective assay of impulsive action that is not affected by anxiety. We hypothesize that the biphasic effect of 8-OH-DPAT is due to actions on presynaptic raphe 5-HT1A autoreceptors, and also postsynaptic 5-HT1A receptors. These results suggest that this receptor mediates impulsive action and that this is not secondary to its role in anxiety.