UC Irvine

This chapter discusses how the complex concept of anhedonia can be operationalized and studied in preclinical models. It provides information about the development of anhedonia in the context of early-life adversity, and the power of preclinical models to tease out the diverse molecular, epigenetic, and network mechanisms that are responsible for anhedonia-like behaviors.Specifically, we first discuss the term anhedonia, reviewing the conceptual components underlying reward-related behaviors and distinguish anhedonia pertaining to deficits in motivational versus consummatory behaviors. We then describe the repertoire of experimental approaches employed to study anhedonia-like behaviors in preclinical models, and the progressive refinement over the past decade of both experimental instruments (e.g., chemogenetics, optogenetics) and conceptual constructs (salience, valence, conflict). We follow with an overview of the state of current knowledge of brain circuits, nodes, and projections that execute distinct aspects of hedonic-like behaviors, as well as neurotransmitters, modulators, and receptors involved in the generation of anhedonia-like behaviors. Finally, we discuss the special case of anhedonia that arises following early-life adversity as an eloquent example enabling the study of causality, mechanisms, and sex dependence of anhedonia.Together, this chapter highlights the power, potential, and limitations of using preclinical models to advance our understanding of the origin and mechanisms of anhedonia and to discover potential targets for its prevention and mitigation.