Dopamine (DA) modulates brain circuitry that supports cognition, reward, motor control, and arousal. Perturbed DA signaling is believed to contribute to addiction, ADHD, schizophrenia, and Parkinson’s disease. The presynaptic DA transporter (DAT) is a major determinant of DA signaling and increasing evidence indicates that altered regulation of DAT may contribute to risk for these disorders. We have pursued the nematode Caenorhabditis elegans as a model system to elucidate novel mechanisms regulating DAT and/or DA signaling. DA is important for swimming behavior in the worm, as ablation of the C. elegans gene encoding DAT (dat-1) results in swimming-induced paralysis (Swip). To determine novel presynaptic regulators of DA signaling, we undertook a chemical mutagenesis screen and identified a mutant, vt34, that exhibits robust DA-dependent Swip. vt34 exhibits biochemical and behavioral phenotypes consist with reduced DAT-1 function, with reversal of Swip observed in vt34 mutants crossed to either cat-2, which encodes the DA biosynthetic enzyme tyrosine hydroxylase, or dop-3, which encodes a D2 subtype DA receptor. Additionally, vt34; dat-1 double mutants exhibit an enhanced Swip phenotype. Unlike dat-1 animals, however, vt34 has altered male tail morphology and reduced body size, which we found arises from a premature stop codon in the Runx transcription factor ortholog RNT-1. rnt-1(ok351) and rnt-1(tm388) mutants, as well as mutations in RNT-1’s binding partner, bro-1, also exhibit Swip. Both bioinformatics and reporter expression studies support the expression of rnt-1 by DA neurons. Lastly, vt34 and rnt-1 mutants exhibit reduced mRNA levels of dat-1 and cat-2, further supporting a role for rnt-1 in regulating pathways that dictate the capacity for DA signaling. This work was supported by NIH awards T32 MH065215 (SBR), F31 MH093102 (JAH) and MH095044 (RDB).