Document Detail


Acute administration of dopaminergic drugs has differential effects on locomotion in larval zebrafish.
MedLine Citation:
PMID:  23274813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Altered dopaminergic signaling causes behavioral changes in mammals. In general, dopaminergic receptor agonists increase locomotor activity, while antagonists decrease locomotor activity. In order to determine if zebrafish (a model organism becoming popular in pharmacology and toxicology) respond similarly, the acute effects of drugs known to target dopaminergic receptors in mammals were assessed in zebrafish larvae. Larvae were maintained in 96-well microtiter plates (1 larva/well). Non-lethal concentrations (0.2-50 μM) of dopaminergic agonists (apomorphine, SKF-38393, and quinpirole) and antagonists (butaclamol, SCH-23390, and haloperidol) were administered at 6 days post-fertilization (dpf). An initial experiment identified the time of peak effect of each drug (20-260 min post-dosing, depending on the drug). Locomotor activity was then assessed for 70 min in alternating light and dark at the time of peak effect for each drug to delineate dose-dependent effects. All drugs altered larval locomotion in a dose-dependent manner. Both the D1- and D2-like selective agonists (SKF-38393 and quinpirole, respectively) increased activity, while the selective antagonists (SCH-23390 and haloperidol, respectively) decreased activity. Both selective antagonists also blunted the response of the larvae to changes in lighting conditions at higher doses. The nonselective drugs had biphasic effects on locomotor activity: apomorphine increased activity at the low dose and at high doses, while butaclamol increased activity at low to intermediate doses, and decreased activity at high doses. This study demonstrates that (1) larval zebrafish locomotion can be altered by dopamine receptor agonists and antagonists, (2) receptor agonists and antagonists generally have opposite effects, and (3) drugs that target dopaminergic receptors in mammals appear, in general, to elicit similar locomotor responses in zebrafish larvae.
Authors:
T D Irons; P E Kelly; D L Hunter; R C Macphail; S Padilla
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-28
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  103     ISSN:  1873-5177     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-05     Completed Date:  2013-10-24     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  792-813     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dopamine Agents / administration & dosage*
Dopamine Agonists / administration & dosage
Dopamine Antagonists / administration & dosage
Dose-Response Relationship, Drug
Larva / drug effects,  physiology
Models, Animal
Motor Activity / drug effects*,  physiology
Receptors, Dopamine / physiology
Zebrafish / physiology*
Grant Support
ID/Acronym/Agency:
T32 DA007244/DA/NIDA NIH HHS; T32 DA007244/DA/NIDA NIH HHS; T32 ES007126/ES/NIEHS NIH HHS; T32 ES007126/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Agents; 0/Dopamine Agonists; 0/Dopamine Antagonists; 0/Receptors, Dopamine
Comments/Corrections

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