We are studying the contribution of dopamine transporters to dopamine dependent neurotransmission and behavior in C. elegans. Dopamine is synthesized by tyrosine hydroxylase, TH (encoded by
cat-2; Lints and Emmons 1999) and packaged into synaptic vesicles by the vesicular monoamine transporter, VMAT (encoded by
cat-1, Duerr et al. 1999). Dopamine stimulation is at least partially terminated by re-uptake by the dopamine plasma membrane transporter, DAT (encoded by
dat-1, Jayanthi et al. 1998). DAT mutants show hyper-stimulation of some dopamine-dependent behaviors, consistent with the persistence of abnormally high levels of extracellular dopamine. Recently, Sanyal et al. (2004) reported that C. elegans TH (
cat-2) or VMAT (
cat-1) mutants have low but significant levels of dopamine at the whole organism level. It is not known whether the dopamine is released by the appropriate neurons. We are examining the function of this residual dopamine with a combination of genetics and behavior. If the residual dopamine in TH mutants is totally without extracellular function, then lack of DAT should have no effect on TH mutants behavior. However, preliminary results suggest that the behavior of the double mutant
cat-2;
dat-1 is not identical to that of either single mutant. Similarly, if the dopamine in VMAT mutants is totally without extracellular function, then lack of DAT should have no effect on VMAT mutants behavior. Again, preliminary results suggest that the behavior of the double mutant
cat-2;
cat-1 is not identical to that of either single mutant. We are continuing to characterize these double mutants in order to understand the significance of the behavioral changes and their relationship to neuronal and vesicular levels of dopamine in this organism. Since serotonin is involved in modulating many of the same behaviors as dopamine, we are also examining the roles of serotonin, thorough the use of additional mutants in serotonin synthesis (
tph-1; Sze et al. 2000) and serotonin re-uptake (
mod-5; Ranganathan et al. 2001).