Wistar Kyoto Rats Display Anhedonia In Consumption but Retain Some Sensitivity to the Anticipation of Palatable Solutions

Abstract

The Wistar Kyoto (WKY) rat has been proposed as a model of depression-like symptoms. However, anhedonia-a reduction in the response to normatively rewarding events-as a central depression symptom has yet to be fully assessed in this model. We compared WKY rats and Wistar controls, with stress-susceptibility examined by applying mild unpredictable stress to a subset of each group. Anhedonia-like behavior was assessed using microstructural analysis of licking behavior, where mean lick cluster size reflects hedonic responses. This was combined with tests of anticipatory contrast, where the consumption of a moderately palatable solution (4% sucrose) is suppressed in anticipation of a more palatable solution (32% sucrose). WKY rats displayed greatly attenuated hedonic reactions to sucrose overall, although their reactions retained some sensitivity to differences in sucrose concentration. They displayed normal reductions in consumption in anticipatory contrast, although the effect of contrast on hedonic reactions was greatly blunted. Mild stress produced overall reductions in sucrose consumption, but this was not exacerbated in WKY rats. Moreover, mild stress did not affect hedonic reactions or the effects of contrast. These results confirm that the WKY substrain expresses a direct behavioral analog of anhedonia, which may have utility for increasing mechanistic understanding of depression symptoms.

Animal Models of Depression: What Can They Teach Us about the Human Disease?

“…WKY rats developed depressive-like behavior in response to acute stress and chronic mild stress as measured by various behavioral tests, demonstrating good face construct and partial predictive validity. These rats demonstrated an increased immobility in the forced swim test (FST) [ 164 , 165 ], decreased activity in the open field test [ 166 , 167 ] and decreased consumption of a sugar-based solution (enhanced anhedonia) [ 168 ]. Depressive-like behavior of WKY rats was slightly attenuated by treatment with tricyclic antidepressants (TCA) [ 173 , 174 ], but was resistant to Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) [ 175 ].…”

“…Demonstrates depression-like behaviors in FST, OF, sucrose preference test [ 164 , 165 , 166 , 167 , 168 ].…”

Anhedonic Type Behavior and Anxiety Profile of Wistar-UIS Rats Subjected to Chronic Social Isolation

“…It was discovered that rats subjected to CSI consumed more 34% SS in both schemes. These results were discussed in light of the effects of CSI upon the animals' reactiveness to highly appetizing concentrations of SS and emphasized the involvement of the dopaminergic system in the nucleus accumbens as a modulator of the incentivizing effects of sucrose (Wright et al, 2020).…”

“…In particular, the Sucrose Preference Test (SPT) has been employed to understand the mechanisms underlying anhedonia. This animal experimentation model is based on the appetitive nature of sweet solutions (Cantora and López Ramírez, 2005;Díaz et al, 2010;Alvarez, 2015), wherein the preference pattern of sucrose solutions (SS) at varying concentrations (0.7%, 1%, 2%, 4%, 5%, 8%, 12%, 16%, 32%, and 35%) is used as an indicator of anhedonic-type behavior (Muscat et al, 1991;Grippo et al, 2003;Cortés et al, 2005;Martínez et al, 2008;Rodríguez et al, 2012;Páez-Ardila and Botelho, 2014;He et al, 2020;Wang et al, 2020;Wright et al, 2020).…”

“…In this context, an array of studies have found that animals subjected to CSI consume a greater quantity of high-concentration SS (24%, 32%, and 34%; Muscat et al, 1991;Hall et al, 1997;Brenes Sáenz et al, 2006;Fornaguera, 2008, 2009;Wright et al, 2020), even when given the option to choose solutions of various concentrations (Sammut et al, 2002;Martínez et al, 2008). Such alternations in reward-sensitivity have been widely found to be related to the mesolimbic dopaminergic system (Fone and Porkess, 2008;Rodrigues et al, 2011;Noschang et al, 2021).…”