The Wistar Kyoto (WKY) rat has long been proposed as an animal model of depressive behavior. Exposure to stress produces symptoms such as anhedonia, psychomotor retardation, ambivalence, and negative memory bias. Autoradiographic studies have revealed significant differences in the density of norepinephrine transporter (NET) and serotonin transporter (5-HTT) sites in several brain regions in WKY rats compared to Sprague-Dawley (S-D) rats. Since the mesolimbic dopamine (DA) system is involved in cognitive, emotional, and motivational behaviors, this study examined the distribution of dopamine transporter (DAT) sites in the brains of WKY compared to Wistar (WIS) and S-D rats. DAT sites were labeled with [3H]-GBR12935 (1 nM), and mazindol (50 microM) was used to define nonspecific binding. Quantitative analysis of the specific binding indicated that WKY rats exhibited significant differences in DAT binding sites in the cell body as well as mesolimbic areas in comparison to WIS and S-D rats. While the binding of [3H]-GBR to DAT sites was significantly decreased in the nucleus accumbens (NAc), the amygdala, the ventral tegmental area (VTA), and the reticular part of the substantia nigra (P<.05), the binding was significantly increased in the hippocampal subregions and the hypothalamus (P<.05) in WKY rats compared to the other two strains. In contrast, no strain differences were found in the caudate-putamen. The observed differences in the density and distribution of DAT sites in WKY rats may lead to altered modulation of synaptic DA levels in the cell body and mesolimbic regions, thereby contributing to the noted depression-like behaviors reported in this rat strain.