No abstract

The Wistar-Kyoto (WKY) rat is a stress-sensitive strain that is prone to depressive-like behavior in various experimental paradigms. While recent work has highlighted a role for dopamine (DA) in the pathology of depression, research on the WKY rat has also suggested that dysfunction of DA pathways may be an important component of the behavior in this strain. Previous work has demonstrated differential patterns of DA transporter sites, DA D2 and D3 receptors in WKY rats compared to control strains. To further this work, the present study utilized autoradiographic analysis of [3H]-SCH23390 binding to DA D1 receptors in various brain regions of naïve male WKY and Wistar (WIS) rats. The results revealed a significant strain difference, with WKY rats demonstrating lower D1 binding in the caudate putamen and regions of the nucleus accumbens (p<0.05). An opposite pattern was found in the substantia nigra pars reticulata where D1 binding was higher in WKY rats compared to WIS rats (p<0.05). Because the D1 receptor represents a critical site where DA acts to modify behavior related to depression, the altered expression of this receptor in the WKY rat found in the present study may be reflective of the depressive susceptibility noted in this strain.

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 [125I]-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.

Aims-Previous studies have shown that the Wistar-Kyoto (WKY) rat strain exhibits depressive symptoms such as anhedonia, psychomotor retardation, ambivalence and negative memory bias following exposure to stress. Given the involvement of excitatory glutamate and inhibitory gamma (γ)-aminobutyric acid (GABA) signaling pathways in influencing depressive behavior, the present study investigated strain differences in the distribution of central N-methyl-D-aspartate (NMDA) and GABA A receptor sites in WKY compared to their inbred counterpart, Wistar (WIS) rats.Main methods-Quantitative autoradiographic analysis was used to map the binding and distribution of NMDA and GABA A receptors in various brain regions in WKY and WIS rats.Key findings-Results indicated a significant difference between the two strains. Lower NMDA receptor binding was found in the anterior cingulate cortex, caudate putmen, nucleus accumbens, CA1 region of the hippocampus and the substantia nigra pars reticulata in WKY compared to WIS rats. Conversely, higher GABA A receptor binding was found in the amygdala, caudate putmen, dentate gyrus, CA2 and CA3 fields of the hippocampus, periaqueductal gray and substantia nigra pars reticulata in WKY compared to WIS rats.Significance-Given that these two rat strains differ in their behavioural, endocrine and neurochemical profile, the observed strain differences in NMDA and GABA A receptor binding suggests that these two neurotransmitter systems may be involved in the depressive and stress sensitive phenotype of the WKY rat strain.