マウス線条体間接路におけるL-DOPA受容体GPR143はD2Rとの連関を介して不安様行動を制御する

抄録

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 performed phenotypic analysis using Gpr143-gene deficient (GPR143-KO) mice. To assess anxiety- and exploration-related behaviors, we employed zero-maze test, and found that time spent in open arms was decreased in GPR143-KO mice when compared to wild-type (WT) mice. The time spent in open arms was also decreased in striatal indirect pathway specific GPR143-KO mice. To investigate the involvement of endogenous L-DOPA, we examined the effect of alpha-methyl-para-tyrosine, a synthetic inhibitor of L-DOPA on mouse behavior. We found that administration of α-MPT at the dose of 3mg/kg (i.p.) decreased the release of L-DOPA without affecting that of dopamine from the dorsal striatum. The administration of α-MPT decreased the time spent in open arms in WT mice, while this effect was not observed in GPR143-KO mice. Furthermore, intraventricular administration of a synthetic peptide, which inhibited the interaction between GPR143 and dopamine D2 receptor (DRD2), increased anxiety-like behavior. These results suggest that L-DOPA regulates anxiety-like behavior through GPR143 and DRD2 coupling in the striatal indirect pathway.