title: Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish.
abstract: The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.
authors.affiliation: Stress Physiology and Research Center (SPaRC), Department of Physiology and Biophysics, Georgetown University Medical School, 3900 Reservoir Road, Washington, DC 20057, USA.
authors.forename: Rupert J
authors.initials: RJ
authors.lastname: Egan
authors.forename: Carisa L
authors.initials: CL
authors.lastname: Bergner
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hart
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cachat
authors.forename: Peter R
authors.initials: PR
authors.lastname: Canavello
authors.forename: Marco F
authors.initials: MF
authors.lastname: Elegante
authors.forename: Salem I
authors.initials: SI
authors.lastname: Elkhayat
authors.forename: Brett K
authors.initials: BK
authors.lastname: Bartels
authors.forename: Anna K
authors.initials: AK
authors.lastname: Tien
authors.forename: David H
authors.initials: DH
authors.lastname: Tien
authors.forename: Sopan
authors.initials: S
authors.lastname: Mohnot
authors.forename: Esther
authors.initials: E
authors.lastname: Beeson
authors.forename: Eric
authors.initials: E
authors.lastname: Glasgow
authors.forename: Hakima
authors.initials: H
authors.lastname: Amri
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zukowska
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D010675:Pheromones / Q000378:metabolism; D013045:Species Specificity; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D010675:Pheromones; D005473:Fluoxetine; D002110:Caffeine; D000431:Ethanol; D006854:Hydrocortisone