Genetic associations of single nucleotide polymorphisms in the l-DOPA receptor (GPR143) gene with severity of nicotine dependence in Japanese individuals, and attenuation of nicotine reinforcement in Gpr143 gene-deficient mice
Daiki Masukawa, Daisuke Nishizawa, Kaori Kanai, Satoshi Kitamura, Yuka Kasahara, Tatsuo Hashimoto, Ryo Takahagi, Junko Hasegawa, Kyoko Nakayama, Naomi Sato, Fumihiko Tanioka, Haruhiko Sugimura, Kazutaka Ikeda, Yoshio Goshima
Abstract
l-3,4-dihydroxyphenylalanine (l-DOPA) is a candidate neurotransmitter. l-DOPA is released by nicotine through nicotinic receptors. Recently, G-protein coupled receptor GPR143, was identified as a receptor for l-DOPA. In this study, genetic association studies between GPR143 genetic polymorphisms and smoking behaviors revealed that the single-nucleotide polymorphism rs6640499, in the GPR143 gene, was associated with traits of smoking behaviors in Japanese individuals. In Gpr143 gene-deficient mice, nicotine-induced hypolocomotion and rewarding effect were attenuated compared to those in wild-type mice. Our findings suggest the involvement of GPR143 in the smoking behaviors.