Nathan Fatima M, Ogawa Satoshi, Parhar Ishwar S
Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
J Neurochem. 2015 Jun;133(6):870-8. doi: 10.1111/jnc.13105. Epub 2015 Apr 17.
Kiss1, a neuropeptide predominantly expressed in the habenula, modulates the serotonin (5-HT) system to decrease odorant cue [alarm substance (AS)]-evoked fear behaviour in the zebrafish. The purpose of this study was to assess the interaction of Kiss1 with the 5-HT system as well as to determine the involvement of the 5-HT receptor subtypes in AS-evoked fear. We utilized 0. 28 mg/kg WAY 100635 (WAY), a selective 5-HT1A receptor antagonist, to observe the effects of Kiss1 administration on AS-evoked fear. We found WAY significantly inhibited the anxiolytic effects of Kiss1 (p < 0.001) with an exception of freezing behaviour. Based on this, we utilized 92.79 mg/kg methysergide, a 5-HT1 and 5-HT2 receptor antagonist, and found that methysergide significantly blocked the anxiolytic effects of Kiss1 in the presence of the AS (p < 0.001). From this, we conclude that Kiss1 modulates AS-evoked fear responses mediated by the 5-HT1A and 5-HT2 receptors. Kiss1 peptide intracranially (IC) administrated has been shown to decrease olfactory, alarm substance (AS)-evoked fear response. Blockade of the 5-HT1A receptor utilizing WAY 100635 (0.28 mg/kg) and the 5-HT1 and 5-HT2 receptor utilizing methysergide (92.79 mg/kg) produced increased AS-evoked fear responses that were unable to be overcome even during the recovery period. Blockade of this 5-HT system followed by Kiss1 administration showed that the peptide was unable to recover the anxiolytic effects upon 5-HT1A blocking using WAY 100635 with the exception of freezing behaviour while methysergide significantly blocked all the anxiolytic effects of Kiss1. These findings implicate that Kiss1 could modulate AS-evoked fear responses mediated by 5-HT1A and 5-HT2 receptors.
Kiss1是一种主要在缰核中表达的神经肽，它调节血清素（5-HT）系统，以减少斑马鱼中气味线索[警报物质（AS）]诱发的恐惧行为。本研究的目的是评估Kiss1与5-HT系统的相互作用，并确定5-HT受体亚型在AS诱发的恐惧中的作用。我们使用0.28mg/kg WAY 100635（WAY），一种选择性5-HT1A受体拮抗剂，来观察给予Kiss1对AS诱发恐惧的影响。我们发现WAY显著抑制了Kiss1的抗焦虑作用（p<0.001），但冻结行为除外。基于此，我们使用92.79mg/kg美西麦角，一种5-HT1和5-HT2受体拮抗剂，发现美西麦角在存在AS的情况下显著阻断了Kiss1的抗焦虑作用（p<0.001）。由此，我们得出结论，Kiss1调节由5-HT1A和5-HT2受体介导的AS诱发的恐惧反应。颅内（IC）给予Kiss1肽已被证明可减少嗅觉、警报物质（AS）诱发的恐惧反应。使用WAY 100635（0.28mg/kg）阻断5-HT1A受体以及使用美西麦角（92.79mg/kg）阻断5-HT1和5-HT2受体，会产生增加的AS诱发的恐惧反应，即使在恢复期也无法克服。阻断该5-HT系统后给予Kiss1表明，除冻结行为外，该肽在使用WAY 100635阻断5-HT1A后无法恢复抗焦虑作用，而美西麦角显著阻断了Kiss1的所有抗焦虑作用。这些发现表明，Kiss1可以调节由5-HT1A和5-HT2受体介导的AS诱发的恐惧反应。
