Immunoreactive signals of GPR143 in the ventral tegmental area, substantia nigra and their trajectories

Abstract

We have reported physiological properties of L-3,4-deoxyphenylalanine (L-DOPA) as a neurotransmitter. Microinjection of nicotine to the ventral tegmental area (VTA) induces the release of L-DOPA as well as dopamine in the nucleus accumbens (NAc) and promotes locomotor activity in freely moving rats. We recently identified GPR 143 as a receptor candidate of L-DOPA. In the present study, we investigated distribution of GPR143 along with nicotinic acetylcholine receptor α4 (α4NR), α7 subunit (α7NR), and tyrosine hydroxylase (TH) expression in the mouse brain. Mice were perfused with paraformaldehyde and frozen sections were prepared. Immunohistochemistry procedures were performed in floating method and visualized with diaminobentidine-based reactions. To investigate anatomical relationship between GPR143 and other molecules, adjacent sections with anatomical landmarks were used. GPR143-immunoreactive signals were observed in some of cells, and these signals were absent in gpr143-deficient mice. The GPR143-positive cells distributed loosely in the VTA and signals tended to be more densely distributed toward substantia nigra compacta. The immunoreactive signals of GPR143, TH, α4 and α7NR were broadly expressed in nerve-fiber-like structure throughout the NAc and the dorsal striatum. These findings suggest a functional coupling between the nicotinic receptors and GPR143. We are now confirming specific GPR143 mRNA signals by in situ hybridization.