Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila

Background: Drugs of abuse have a common property in mammals, which is thei r ability to facilitate the release of the neurotransmitter and neuromodula tor dopamine in specific brain regions involved in reward and motivation. T his increase in synaptic dopamine levels is believed to act as a positive r einforcer and to mediate some of the acute responses to drugs. The mechanis ms by which dopamine regulates acute drug responses and addiction remain un known. Results: We present evidence that dopamine plays a role in the responses of Drosophila to cocaine, nicotine or ethanol. We used a startle-induced nega tive geotaxis assay and a locomotor tracking system to measure the effect o f psychostimulants on fly behavior. Using these assays, we show that acute responses to cocaine and nicotine are blunted by pharmacologically induced reductions in dopamine levels. Cocaine and nicotine showed a high degree of synergy in their effects, which is consistent with an action through conve rgent pathways. In addition, we found that dopamine is involved in the acut e locomotor-activating effect, but not the sedating effect, of ethanol. Conclusions: We show that in Drosophila, as in mammals, dopaminergic pathwa ys play a role in modulating specific behavioral responses to cocaine, nico tine or ethanol. We therefore suggest that Drosophila can be used as a gene tically tractable model system in which to study the mechanisms underlying behavioral responses to multiple drugs of abuse.