IMMUNOGOLD LOCALIZATION OF THE DOPAMINE TRANSPORTER - AN ULTRASTRUCTURAL-STUDY OF THE RAT VENTRAL TEGMENTAL AREA (VOL 17, PG 4037, 1997)

The dopamine transporter (DAT) plays an important role in the plasmale mmal reuptake of dopamine and, thus, in the termination of normal dopa minergic neurotransmission. DAT is also a major binding site for cocai ne and other stimulants, the psychoactive effects of which are associa ted primarily with the inhibition of dopamine reuptake within mesocort icolimbic dopaminergic neurons. We used electron microscopy with an an ti-peptide antiserum directed against the N-terminal domain of DAT to determine the subcellular localization of this transporter in the rat ventral tegmental area (VTA), the region that contains the cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA, almost 95% of the DAT immunogold-labeled profiles are neuronal perika rya and dendrites, and the remainder are unmyelinated axons. Within pe rikarya and large proximal dendrites, almost all of the DAT immunogold particles are associated with intracellular membranes, including sacc ules of Golgi and cytoplasmic tubulovesicles. In contrast, within medi um-to small-diameter dendrites and unmyelinated axons, most of the DAT gold particles are located on plasma membranes. In dually labeled tis sue, peroxidase reaction product for the catecholamine-synthesizing en zyme tyrosine hydroxylase is present in DAT-immunoreactive profiles. T hese findings suggest that intermediate and distal dendrites are both the primary sites of dopamine reuptake and the principal targets of co caine and related psychostimulants within dopaminergic neurons in the VTA.