PUBLICATION
Behavioral analysis of dopaminergic activation in zebrafish and rats reveals similar phenotypes
- Authors
- Ek, F., Malo, M., Åberg Andersson, M., Wedding, C., Kronborg, J., Svensson, P., Waters, S., Petersson, P., Olsson, R.
- ID
- ZDB-PUB-160308-6
- Date
- 2016
- Source
- ACS Chemical Neuroscience 7(5): 633-46 (Journal)
- Registered Authors
- Keywords
- Zebrafish, dopamine agonist, behavioral model, receptor binding site, apomorphine
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Apomorphine/metabolism
- Apomorphine/pharmacology
- Dopamine/metabolism*
- Dopamine Agonists/metabolism
- Dopamine Agonists/pharmacology
- Dopamine Antagonists/metabolism
- Dopamine Antagonists/pharmacology
- Dose-Response Relationship, Drug
- Humans
- Locomotion/drug effects
- Locomotion/physiology*
- Male
- Phenotype*
- Protein Binding/physiology
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Rats
- Rats, Sprague-Dawley
- Receptors, Dopamine/chemistry*
- Receptors, Dopamine/metabolism*
- Zebrafish
- PubMed
- 26947759 Full text @ ACS Chem. Neurosci.
Citation
Ek, F., Malo, M., Åberg Andersson, M., Wedding, C., Kronborg, J., Svensson, P., Waters, S., Petersson, P., Olsson, R. (2016) Behavioral analysis of dopaminergic activation in zebrafish and rats reveals similar phenotypes. ACS Chemical Neuroscience. 7(5):633-46.
Abstract
Zebrafish is emerging as a complement to mammals in behavioral studies, however there is a lack of comparative studies with rodents and humans to establish the zebrafish as a predictive translational model. Here we present a detailed phenotype evaluation of zebrafish larvae, measuring 300-3000 variables and analyzing them using multivariate analysis to identify the most important ones for further evaluations. The dopamine agonist apomorphine has previously been shown to have a complex U-shaped dose-response relationship in the variable distance travelled. In this study, we focused on breaking down distance travelled into more detailed behavioral phenotypes for both zebrafish and rats and identified in the multivariate analysis low and high dose phenotypes with characteristic behavioral features. Further analysis of single parameters also identified an increased activity at the lowest concentration indicative of a U-shaped dose-response. Apomorphine increased the distance of each swim movement (bout) at both high and low doses, but the underlying behavior of this increase is different; at high dose both bout duration and frequency increased whereas bout max speed was higher at low dose. Larvae also displayed differences in place preference. The low dose phenotype spent more time in the center, indicative of an anxiolytic effect, while the high-dose phenotype had a wall preference. These dose-dependent effects corroborated findings in a parallel rat study and previous observations in humans. The translational value of pharmacological zebrafish studies was further evaluated by comparing the amino acid sequence of the dopamine receptors (D1-D4), between zebrafish, rats and humans. Humans and zebrafish share 100% of the amino acids in the binding site for D1 and D3 whereas D2 and D4 receptors share 85-95%. Molecular modeling of dopamine D2 and D4 receptors indicated that non-conserved amino acids have limited influence on important ligand-receptor interactions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping