L-DOPA receptor, GPR143, is involved in methylphenidate -induced locomotion in mice

Abstract

Methylphenidate(MPH) is widely known as a drug for attention deficit hyperactivity disorder as well as an addictive drug, and its main pharmacological action is thought to elevates extracellular dopamine(DA) level by inhibiting presynaptic DA transporter. L-3.4-dihydroxyphenylalanine(DOPA) has been believed as a precursor of DA. We proposed that DOPA itself acts as neurotransmitter. We previously demonstrated that nicotine, and methamphetamine (METH) that shares pharmacological properties with MPH, increased not only extracellular DA level but also DOPA level in the nucleus accumbens of mice, while cocaine increased the DA but suppressed the DOPA level. Recently we identified G protein coupled receptor GPR143, a gene product of ocular albinism-1, as a receptor for DOPA. We showed that GPR143 was involved in the pharmacological actions of nicotine (Masukawa et al, 2020). In this study, we compared actions of MPH between wild-type (Wt) and Gpr143 gene-deficient (Gpr143^-/y) mice. MPH-treated mice showed an increase in locomotor activity compared to the saline-treated group. This effect was attenuated in Gpr143^-/y mice. Cocaine-treated mice also showed an increase in locomotor activity in Wt and Gpr143^-/y mice compared to corresponding controls, but there was no difference in this effect between Wt and Gpr143^-/y mice. These results suggest that GPR143 is involved in the pharmacological action of MPH.