Dopamine tone regulates D1 receptor trafficking and delivery in striatal neurons in dopamine transporter-deficient mice

In vivo, G protein-coupled receptors (GPCR) for neurotransmitters undergo c omplex intracellular trafficking that contribute to regulate their abundanc e at the cell surface. Here, we report a previously undescribed alteration in the subcellular localization of D1 dopamine receptor (D1R) that occurs i n vivo in striatal dopaminoceptive neurons in response to chronic and const itutive hyperdopaminergia. Indeed, in mice lacking the dopamine transporter , D1R is in abnormally low abundance at the plasma membrane of cell bodies and dendrites and is largely accumulated in rough endoplasmic reticulum and Golgi apparatus. Decrease of striatal extracellular dopamine concentration with B-hydroxydopamine (6-OHDA) in heterozygous mice restores delivery of the receptor from the cytoplasm to the plasma membrane in cell bodies. Thes e results demonstrate that, in vivo, in the central nervous system, the sto rage in cytoplasmic compartments involved in synthesis and the membrane del ivery contribute to regulate GPCR availability and abundance at the surface of the neurons under control of the neurotransmitter tone. Such regulation may contribute to modulate receptivity of neurons to their endogenous liga nds and related exogenous drugs.