We propose that L-DOPA by itself is a neurotransmitter. Recently, a G-protein coupled receptor GPR143, a gene product of ocular-albinism1, was identified as a receptor for L-DOPA. In this study, to identify the physiological role of GPR143, we examined the phenotypic analysis using Gpr143-gene deficient (GPR143-KO) mice. We found that time spent in open arms using zero-maze test was decreased in GPR143-KO mice when compared to wild-type (WT) mice. The time spent in open arms was also decreased in indirect pathway striatal neuron specific GPR143-KO mice. To investigate the involvement of endogenous L-DOPA in this phenotype, we perform zero-maze test after treatment with alpha-methyl-para-tyrosine (α-MPT), a synthetic inhibitor of L-DOPA. Intraperitoneal injection of α-MPT at the dose of 3 mg/kg, which decreased the striatal content of L-DOPA without affecting that of dopamine, suppressed the time spent in open arms in WT mice. This effect of α-MPT was not observed in GPR143-KO mice. These results suggest that L-DOPA regulates anxiety-like behavior through GPR143 expressed in the striatal indirect pathway neurons.