Figure 5. A model for LN_v and dLMO regulation of cocaine sensitivity in Drosophila.

(A) In wild type, LN_vs modulate locomotor responses via electrical activity and synaptic transmission. In this model, cocaine would act to directly increase LN_v activity. Upon cocaine administration, synaptic dopamine concentrations would be increased (via cocaine's inhibition of the plasma membrane dopamine transporter), and activation of presumed dopamine receptors on the LN_v (dark arrowheads) would stimulate electrical activity and subsequent synaptic output. This activity would then contribute to the behavioral response of the fly to cocaine. (B) LN_v ablations eliminate LN_v contribution to the cocaine response, reducing cocaine sensitivity. (C) dLmo loss–of–function mutants (dLmo^LOF), which have increased cocaine sensitivity, would have increased activity/output during the cocaine response. This increased activity may be mediated by increases in dopamine receptor content on the LN_v. (D) dLmo^GOF mutants would have reduced LN_v output and reduced cocaine sensitivity. This could result from a reduction in dopamine receptor density. (Tsai et al., 2004; reprinted with permission)