title: The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development.
abstract: Exposure to moderate levels of ethanol during brain development has a number of effects on social behavior but the molecular mechanisms that mediate this are not well understood. Gaining a better understanding of these factors may help to develop therapeutic interventions in the future. Zebrafish offer a potentially useful model in this regard. Here, we introduce a zebrafish model of moderate prenatal ethanol exposure. Embryos were exposed to 20mM ethanol for seven days (48hpf-9dpf) and tested as adults for individual social behavior and shoaling. We also tested their basal anxiety with the novel tank diving test. We found that the ethanol-exposed fish displayed reductions in social approach and shoaling, and an increase in anxiety in the novel tank test. These behavioral differences corresponded to differences in hrt1aa, slc6a4 and oxtr expression. Namely, acute ethanol caused a spike in oxtr and ht1aa mRNA expression, which was followed by down-regulation at 7dpf, and an up-regulation in slc6a4 at 72hpf. This study confirms the utility of zebrafish as a model system for studying the molecular basis of developmental ethanol exposure. Furthermore, it proposes a putative developmental mechanism characterized by ethanol-induced OT inhibition leading to suppression of 5-HT and up-regulation of 5-HT1A, which leads, in turn, to possible homeostatic up-regulation of 5-HTT at 72hpf and subsequent imbalance of the 5-HT system.
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Parker
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
authors.forename: Leonette V
authors.initials: LV
authors.lastname: Annan
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
authors.forename: Alexandros H
authors.initials: AH
authors.lastname: Kanellopoulos
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Brock
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
authors.forename: Fraser J
authors.initials: FJ
authors.lastname: Combe
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
authors.forename: Matteo
authors.initials: M
authors.lastname: Baiamonte
authors.affiliation: Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, United Kingdom.
authors.forename: Muy-Teck
authors.initials: MT
authors.lastname: Teh
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom. Electronic address: c.h.brennan@qmul.ac.uk.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Brennan
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012919:Social Behavior; D013315:Stress, Psychological / Q000503:physiopathology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D000431:Ethanol
keywords: Moderate prenatal ethanol; Oxytocin; Serotonin; Social; Vasopressin; Zebrafish