Involvement of the L-DOPA receptor GPR143 in acute and chronic actions of methylphenidate

Methylphenidate (MPH) and methamphetamine (METH) are the current treatments of choice for attention deficit/hyperactivity disorder. We previously reported that METH induces the release of dopamine (DA) and of the neurotransmitter candidate L-3,4-dihydroxyphenylalanine (L-DOPA). In contrast, we here found that MPH increased the DA release while it did not affect the L-DOPA release from the dorsolateral striatum. Nevertheless, MPH-induced hyperlocomotion was reduced in Gpr143 (LDOPA receptor) gene-deficient (Gpr143-/y) mice. The rewarding effect and increased c-fos expression induced by MPH were also attenuated in Gpr143-/y mice. Together, these findings suggest that GPR143 is involved in the acute and chronic actions of MPH. (c) 2023 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Automated summary

Methylphenidate (MPH) and methamphetamine (METH) are commonly used for treating attention deficit/hyperactivity disorder. MPH increases dopamine (DA) release but has no effect on L-DOPA release, while METH induces the release of both DA and L-DOPA. However, MPH-induced hyperlocomotion and rewarding effects are reduced in mice lacking the Gpr143 (LDOPA receptor) gene. These findings indicate the involvement of GPR143 in the actions of MPH.