The Wistar-Kyoto (WKY) rat has been proposed as an animal model of depressive behavior and exhibits hyper-responsiveness to stressful stimulation when compared to other rat strains. We have demonstrated that WKY rats consume 200% more alcohol under naïve conditions as compared to their outbred counterparts, Wistar (WIS) rats. The present study was designed to understand the influence of stress and alcohol consumption on central dopamine type-2 (D2) receptor sites in these two behaviorally distinct rat strains. The first part of this study examined the effects of chronic stress on alcohol consumption, while the second part examined the binding of [(125)I]-Iodosulpiride to D2 receptors in control, stressed or stress and alcohol co-treated WKY compared to WIS rats. Exposure to chronic stress led to an increase in the amount of alcohol consumed by both rat strains, with WKY rats consuming significantly more alcohol than WIS rats with or without stress exposure. Quantitative autoradiography experiments showed that chronic stress increased D2 receptor binding in the caudate putamen (CPu), nucleus accumbens (NAc), substantia nigra (SN) and ventral tegmental area (VTA) of WKY rats, and reduced receptor binding in the CPu and SN of WIS rats. Compared to the stressed animals, WKY rats co-treated with stress and alcohol demonstrated a reduction in D2 receptor sites in the cell body regions (SN and VTA), while WIS rats showed no changes in receptor binding. The observed changes in D2 receptor sites may indicate altered DA neurotransmission following stress and alcohol exposure. Since stressed WKY rats consumed more alcohol, it is possible that consumption of alcohol reverses the stress-induced D2 receptor alterations in the cell body regions, suggestive of a self medicating phenotype.