Intranasal delivery of drugs to the central nervous system of adult zebrafish

Abstract

The small teleost zebrafish (Danio rerio) has become a critically important laboratory animal in biomedicine. One of their key practical advantages, the convenient method of small-molecule administration via water immersion, has certain problems with dosing precision and drug delivery. Here, we present a simple protocol for the intranasal delivery of neuroactive drugs in adult zebrafish using arecoline and nicotine, two well-studied reference neuroactive drugs chosen for the proof of concept. Adult fish received 1 μL water solution of arecoline (1 and 10 mg/mL) or nicotine tartrate (5 and 10 mg/mL) or the same volume of drug-free water (control) into both nostrils, followed by behavioral testing in the novel tank test 5 min later. Mass spectrometry analyses confirmed that both drugs rapidly reached the zebrafish brain following intranasal administration. Intranasally administered arecoline (10 mg/mL) and nicotine (5 and 10 mg/mL) demonstrated overt behavioral profiles, evoking characteristic anxiolytic-like effects in zebrafish similar to those observed here for a standard 20-min water immersion method (10 mg/L arecoline or 30 mg/L nicotine). Overall, we showed that neuroactive drugs can be delivered to adult zebrafish intranasally to exert central effects, which may (at least for some drugs) occur faster and can need smaller drug quantities than for the water immersion delivery.