Serotonin (5-HT) receptors have been implicated in responses to aversive stimuli in mammals and fish, but its precise role is still unknown. Moreover, since at least seven families of 5-HT receptors exist in vertebrates, the role of specific receptors is still debated. Aversive stimuli can be classified as indicators of proximal, distal, or potential threat, initiating responses that are appropriate for each of these threat levels. Responses to potential threat usually involve cautious exploration and increased alertness, while responses to distal and proximal threat involve a fight-flight-freeze reaction. We exposed adult zebrafish to a conspecific alarm substance (CAS) and observed behavior during (distal threat) and after (potential threat) exposure, and treated with the 5-HT_2C receptor agonists MK-212 or WAY-161503 or with the antagonist RS-102221. The agonists blocked CAS-elicited defensive behavior (distal threat), but not post-exposure increases in defensive behavior (potential threat), suggesting inhibition of responses to distal threat. MK-212 blocked changes in freezing elicited by acute restraint stress, a model of proximal threat, while RS-102221 blocked changes in geotaxis elicited this stressor. We also found that RS-102221, a 5-HT_2C receptor antagonist, produced small effect on behavior during and after exposure to CAS.

Preprint: https://www.biorxiv.org/content/10.1101/2020.10.04.324202; Data and scripts: https://github.com/lanec-unifesspa/5-HT-CAS/tree/master/data/5HT2C

血清素 (5-HT) 受体与哺乳动物和鱼类对厌恶刺激的反应有关，但其确切作用仍不清楚。此外，由于脊椎动物中至少存在 7 个 5-HT 受体家族，因此特定受体的作用仍存在争议。厌恶刺激可以分类为近端、远端或潜在威胁的指标，启动适合这些威胁级别中的每一个的响应。对潜在威胁的反应通常涉及谨慎探索和提高警觉性，而对远端和近端威胁的反应涉及战斗-飞行-冻结反应。我们将成年斑马鱼暴露于同种警报物质 (CAS) 中，并观察了在（远端威胁）和之后（潜在威胁）暴露期间的行为，并用 5-HT _2C治疗受体激动剂 MK-212 或 WAY-161503 或拮抗剂 RS-102221。激动剂阻断了 CAS 引发的防御行为（远端威胁），但不阻断暴露后防御行为（潜在威胁）的增加，这表明抑制了对远端威胁的反应。MK-212 阻止了由急性约束压力引起的冻结变化，这是一种近端威胁模型，而 RS-102221 阻止了引起这种压力源的趋地性变化。我们还发现，5-HT _2C受体拮抗剂 RS-102221 在暴露于 CAS 期间和之后对行为的影响很小。

预印本：https://www.biorxiv.org/content/10.1101/2020.10.04.324202；数据和脚本：https://github.com/lanec-unifesspa/5-HT-CAS/tree/master/data/5HT2C