Immunocytochemical localization of the dopamine transporter in human brain

The dopamine transporter (DAT) was localized in normal human brain tissue b y light microscopic immunocytochemistry by using highly specific monoclonal antibodies. Regional distribution of DAT was found in areas with establish ed dopaminergic circuitry, e.g., mesostriatal, mesolimbic, and mesocortical pathways. Mesencephalic DAT-immunoreactivity was enriched in the dendrites and cell bodies of neurons in the substantia nigra pars compacta and ventr al tegmental area. Staining in the striatum and nucleus accumbens was dense and heterogeneous. Mesocortical DAT immunoreactivity in motor, premotor, a nterior cingulate, prefrontal, entorhinal/perirhinal, insular, and visual c ortices was detected in scattered varicose and a few nonvaricose fibers. Va ricose fibers were relatively enriched in the basolateral and central subnu clei of amygdala, with sparser fibers in lateral and basomedial subnuclei. Double-labeling studies combining DAT and tyrosine hydroxylase (TH) immunos taining in the ventral mesencephalon showed two subpopulations of dopaminer gic neurons differentiated by the presence or absence of DAT-immunoreactivi ty in the A9 and A10 cell groups. In other dopaminergic cell groups (A11, A 13-A15), TH-positive hypothalamic neurons showed no detectable DAT-immunore activity. However, fine DAT-immunoreactive axons were scattered throughout the hypothalamus, particularly concentrated along the medial border, with m ore coarse axons present along the lateral border. These findings demonstra te that most mesotelencephalic dopamine neurons of human brain express high levels of DAT throughout their entire somatodendritic and axonal domains, whereas a smaller subpopulation of mesencephalic dopamine cells and all hyp othalamic dopamine cell groups examined express little or no DAT These data indicate that different subpopulations of dopaminergic neurons use differe nt mechanisms to regulate their extracellular dopamine levels. (C) 1999 Wil ey-Liss, Inc.