title: Kisspeptin1 modulates odorant-evoked fear response via two serotonin receptor subtypes (5-HT1A and 5-HT2) in zebrafish.
abstract: 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.
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
authors.forename: Fatima M
authors.initials: FM
authors.lastname: Nathan
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
authors.forename: Satoshi
authors.identifier: http://orcid.org/0000-0001-6664-4448
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
authors.forename: Ishwar S
authors.initials: IS
authors.lastname: Parhar
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D059648:Kisspeptins / Q000378:metabolism*; D008297:Male; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D059648:Kisspeptins; D044348:Receptors, Serotonin, 5-HT2; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D029961:Zebrafish Proteins; D044282:Receptor, Serotonin, 5-HT1A
keywords: WAY 100635; geriseum centrale; methysergide; olfactory; raphe