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Chronic Social Defeat and Intracranial Self-Stimulation: Unmasking the Many Faces of Depression?

      Depression is a highly complex psychiatric disorder owing in part to the great variability in patient symptoms; treatment response; and, presumably, underlying biological mechanisms (
      • Nestler E.J.
      • Hyman S.E.
      Animal models of neuropsychiatric disorders.
      ). This complexity as well as the inherent difficulty in studying mental symptoms in rodents has made depression very difficult to model in the laboratory. Chronic social defeat stress (CSDS) offers construct, face, and predictive validity; it induces many of the core symptoms of depression that are measurable in rodents. This ethologically relevant stressor involves forcing a rodent to intrude on the home cage of a larger, more aggressive rodent, which overpowers it until a rapidly submissive phenotype emerges (a process that is repeated typically for ≥10 days). Anhedonia, the lack of interest in pleasurable or rewarding stimuli, is one of the most common symptoms of depression. In rodents, anhedonia is often characterized by a reduction in preference for sucrose. Anhedonia reportedly is induced by CSDS, yet results from sucrose preference tests are inconsistent among studies. The test is vulnerable to various factors that may influence an animal’s behavior, such as neophobia or a state of satiety. A promising solution to this conundrum is intracranial self-stimulation (ICSS), a powerful assay used to assess reward sensitivity that appears unaffected by confounds often seen in other reward-related tests. In this issue of Biological Psychiatry, two studies, for the first time, combine CSDS with ICSS to determine whether 1) CSDS produces anhedonia as reflected in changing thresholds for ICSS, 2) CSDS produces maladaptive changes in brain reward processing, and 3) antidepressant treatment can reverse CSDS-induced deficits in reward functioning.
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