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Review
. 2018 Nov 1;21(11):1049-1065.
doi: 10.1093/ijnp/pyy083.

Making Sense of Rodent Models of Anhedonia

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Free PMC article
Review

Making Sense of Rodent Models of Anhedonia

Simona Scheggi et al. Int J Neuropsychopharmacol. .
Free PMC article

Abstract

A markedly reduced interest or pleasure in activities previously considered pleasurable is a main symptom in mood disorder and psychosis and is often present in other psychiatric disorders and neurodegenerative diseases. This condition can be labeled as "anhedonia," although in its most rigorous connotation the term refers to the lost capacity to feel pleasure that is one aspect of the complex phenomenon of processing and responding to reward. The responses to rewarding stimuli are relatively easy to study in rodents, and the experimental conditions that consistently and persistently impair these responses are used to model anhedonia. To this end, long-term exposure to environmental aversive conditions is primarily used, and the resulting deficits in reward responses are often accompanied by other deficits that are mainly reminiscent of clinical depressive symptoms. The different components of impaired reward responses induced by environmental aversive events can be assessed by different tests or protocols that require different degrees of time allocation, technical resources, and equipment. Rodent models of anhedonia are valuable tools in the study of the neurobiological mechanisms underpinning impaired behavioral responses and in the screening and characterization of drugs that may reverse these behavioral deficits. In particular, the antianhedonic or promotivational effects are relevant features in the spectrum of activities of drugs used in mood disorders or psychosis. Thus, more than the model, it is the choice of tests that is crucial since it influences which facets of anhedonia will be detected and should be tuned to the purpose of the study.

Figures

Figure 1.
Figure 1.
Rodent models of depression/anhedonia and behavioral tests used to evaluate reactivity toward aversive (a) and positive stimuli (b). The figure represents 2 of the most commonly used models that induce depressive- and anhedonic-like behaviors in rodents (chronic mild stress and chronic social defeat) and the behavioral tests primarily applied to these models to evaluate the reactivity toward aversive (a, behavioral despair) and rewarding stimuli (b, anhedonia). The chronic mild stress model of depression relies on a series of mild physical stressors that are presented in an unpredictable sequence for 5 to 9 weeks. The chronic social defeat model relies on an innate social behavior in adult male rodents that show a strong motivation to defend their territory (resident) against an unfamiliar male (intruder). The stronger resident predictably defeats the intruder and a stable dominant/subordinate relationship is formed. In the chronic protocol, the intruder is periodically subordinated by the territorially aggressive resident over a couple to several weeks.
Figure 2.
Figure 2.
Schematic representation of some of the behavioral tests used to assess deficits in the responses to reward in rodents. In the hedonic taste reactivity test (a), affective reactions to a palatable sucrose solution are measured. In the sucrose consumption or preference test (b), the choice between a sweet solution and water is determined. In the conditioned place preference protocol (c), the preference for the chamber where the rewarding stimulus was previously presented compared with the neutral chamber is evaluated. In the social interaction test (d), the amount of time spent in proximity to a social compared with an inanimate target is determined. In the intracranial self stimulation protocol (e), the operant behavior that allows animals to self-stimulate specific regions in the brain reward circuitry by pressing a lever or turn a wheel is evaluated. In the sucrose self-administration protocol (g), the operant behavior that allows animals to self-administer a palatable food by pressing a lever is evaluated.

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