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Dopaminergic Neuromodulation in Short-term Sensitization by an Aversive Chemical Stimulus in Larval Zebrafish (Danio rerio)

Abstract

Zebrafish (Danio rerio) hold immense promise for the study of learning and memory. Several attractive properties characterize this vertebrate animal model. For instance, zebrafish possesses a relatively reduced neural circuitry, which facilitates the drawing of causal relationships between changes on the behavioral scale to changes on the cellular-molecular level. They can also be affected by and absorb pharmacological agents in bath, and undergo learning and memory paradigms as early as 5 days post-fertilization (dpf). In particular, following a brief introduction of a noxious stimulus, allyl isothiocyanate (mustard oil, MO), 5-6 dpf zebrafish exhibit short-term sensitization. This memory has been demonstrated behaviorally through increased thigmotaxis and locomotion. However, the neuromodulatory mechanisms behind this non-declarative, non-associative form of memory remains to be elucidated. Exploiting this animal model’s strengths, we placed zebrafish under high-throughput pharmacological dissections with dopamine-receptor antagonists SCH-23390, eticlopride hydrochloride, haloperidol, and L-745,870 trihydrochloride in order to determine the role of dopamine and delineate receptor subtype-specific influences. These blockades have not only confirmed the role of dopamine, but also have demonstrated a differential involvement of the receptor subtypes within the two behaviors. Nonetheless, further investigations are required in order to determine the influence of other neuromodulators in the establishment of MO-induced short-term sensitization.

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