Acute administration of dopaminergic drugs has differential effects on locomotion in larval zebrafish

• Published in: Pharmacology, biochemistry and behavior Vol. 103; no. 4; pp. 792 - 813
• Main Authors: Irons, T.D., Kelly, P.E., Hunter, D.L., MacPhail, R.C., Padilla, S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2013
• Subjects: Acute; Animals; Dopamine; Dopamine Agents - administration & dosage; Dopamine Agonists - administration & dosage; Dopamine Antagonists - administration & dosage; Dose-Response Relationship, Drug; Larva - drug effects; Larva - physiology; Locomotor activity; Models, Animal; Motor Activity - drug effects; Motor Activity - physiology; Receptor; Receptors, Dopamine - physiology; Zebrafish; Zebrafish - physiology; Zebrafish; Dopamine; Receptor; Acute; Locomotor activity
• DOI: 10.1016/j.pbb.2012.12.010
• ISSN: 0091-3057

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 (0.2–50μM) of dopaminergic agonists (apomorphine, SKF-38393, and quinpirole) and antagonists (butaclamol, SCH-23390, and haloperidol) were administered at 6days post-fertilization (dpf). An initial experiment identified the time of peak effect of each drug (20–260min post-dosing, depending on the drug). Locomotor activity was then assessed for 70min 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. ► Larval locomotion was altered by dopamine receptor agonists and antagonists. ► Receptor agonists and antagonists generally had opposite effects. ► Larval zebrafish are promising models for dopamine behavioral pharmacology.