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Abstract
Pathology of reward processing is a major clinical feature of stress-related neuropsychiatric disorders including depression. Several dimensions of reward processing can be impacted, including reward valuation/salience, learning, expectancy and effort valuation. To establish the causal relationships between stress, brain changes, and reward processing pathologies, valid animal models are essential. Here, we present mouse experiments investigating behavioral effects of chronic social stress (CSS) in association learning tests of gustatory reward salience and effort valuation. The reward salience test (RST) comprised Pavlovian pairing of a tone with gustatory reward. The effort valuation test (EVT) comprised operant responding for gustatory reinforcement on a progressive ratio schedule (PRS). All testing was conducted with mice at 100% baseline body weight (BBW). In one experiment, mice underwent 15-day CSS or control handling (CON) and testing was conducted using sucrose pellets. In the RST on days 16–17, CSS mice made fewer feeder responses and had a longer tone response latency, than CON mice. In a shallow EVT on days 19–20, CSS mice attained a lower final ratio than CON mice. In a second CSS experiment, mice underwent CSS or CON and testing was conducted with chocolate pellets and in the presence of standard diet (low effort/low reward). In the RST on days 16–18, CSS mice made fewer feeder responses and had a longer tone response latency, than CON mice. In a steep EVT on days 19–20, CSS and CON mice attained less pellets than in the RST, and CSS mice attained a lower final ratio than CON mice. At day 21, blood levels of glucose and the satiety adipokine leptin were similar in CSS and CON mice. Therefore, CSS leads to consistent reductions in reward salience and effort valuation in tests based on association learning. These reward pathology models are being applied to identify the underlying neurobiology and putative molecular targets for therapeutic pharmacology.
Highlights
Stressful life events are major etiological factors for prevalent neuropsychiatric disorders, including depression
We report in mice that chronic social stress (CSS) leads to deficits in behavioral tests for the dimensions of reward salience and effort valuation relative to gustatory stimuli, and identify some test variables that are important in determining the robustness of these CSS effects
In Experiments 1 and 3, CSS mice obtained less sweet pellets than control handling (CON) mice, due to a longer response latency during the conditioned stimulus (CS). This deficit was consistent across sessions, both CON and CSS mice obtained more rewards as they progressed through trials/sessions
Summary
Stressful life events are major etiological factors for prevalent neuropsychiatric disorders, including depression. Depression is heterogeneous with respect to symptomatology, as are other stress-related neuropsychiatric disorders such as schizophrenia. A core symptom of depression is described as markedly reduced interest or pleasure in (almost) all activities most of the day nearly every day (Dichter et al, 2010). Impaired processing of rewarding events/stimuli characterizes negative symptoms in schizophrenia (Dichter et al, 2010; Hartmann et al, 2015). The research domain criteria (RDoC) framework places focus on the study and understanding of specific psychological processes, the dysfunction of which is relevant to one or more neuropsychiatric disorders, i.e., transdiagnostic (Cuthbert and Insel, 2013). The research domain criteria (RDoC) framework places focus on the study and understanding of specific psychological processes, the dysfunction of which is relevant to one or more neuropsychiatric disorders, i.e., transdiagnostic (Cuthbert and Insel, 2013). ‘‘Positive valence systems’’ is the RDoC term for constructs underlying reward-stimulus processing, and examples include: valuation of the salience of a prospective reward (anticipation); learning the association between neutral stimuli and reward (Pavlovian learning), or behavioral actions and reward (operant learning); reward expectancy triggered by stimuli associated with reward; effortful motivation to obtain reward
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