Drosophila Dopamine2-like Receptors Function as Autoreceptors

摘要

Dopaminergic signaling pathways are conserved between mammals and Drosophila, and D2 receptors have been identified in Drosophila. However, it has not been demonstrated whether Drosophila D2 receptors function as autoreceptors and regulate the release of dopamine. The goal of this study was to determine if Drosophila D2 receptors act as autoreceptors by probing the extent to which D2 agonists and antagonists affect evoked dopamine release. Fast-scan cyclic voltammetry was used to measure stimulated dopamine release at a carbon-fiber microelectrode implanted in an intact, larval Drosophila nervous system. Dopamine release was evoked using 5 s blue-light stimulations that open Channelrhodopsin-2, a blue-light-activated cation channel that was specifically expressed in dopaminergic neurons. In mammals, administration of a D2 agonist decreases evoked dopamine release by increasing autoreceptor feedback. Similarly, we found that the D2 agonists bromocriptine and quinpirole decreased stimulated dopamine release in Drosophila. D2 antagonists were expected to increase dopamine release, and the D2 antagonists flupenthixol,butaclamol, and haloperidol did increase stimulated release. Agonistsdid not significantly modulate dopamine uptake, although the modulatoryeffects of D2 drugs on release were affected by prior administrationof the uptake inhibitor nisoxetine. These results demonstrate thatthe D2 receptor functions as an autoreceptor in Drosophila. The similarities in dopamine regulation validate Drosophila as a model system for studying the basic neurobiology of dopaminergicsignaling.