Developmental Trajectories of Anhedonia in Preclinical Models

Abstract

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 anhedonialike behaviors in preclinical models, and the progressive refinement over the past decade of both experimental instruments (e.g., chemogenetics, optogenetics) and

Behavioral responses to natural rewards in developing male and female rats

“…Loss of interest in rewarding activities (i.e., anhedonia) is a core symptom of many psychiatric disorders, including mood and psychotic disorders (Barch et al., 2016; Lambert et al., 2018; Nusslock & Alloy, 2017). Similar motivational deficits have been recapitulated in rodent models useful for the study of depression and schizophrenia, including rodent models of early life stress (ELS) (Birnie et al., 2022; Duque‐Quintero et al., 2022; Rincon‐Cortes, 2023; Scheggi et al., 2018; Slaney et al., 2018; Young & Markou, 2015). Although sex differences in reward‐related responses have been reported in adult animals following ELS (Birnie et al., 2022; Rincon‐Cortes, 2023; Williams et al., 2022), less is known regarding the normative development of reward‐related responses in both sexes.…”

“…Loss of interest in rewarding activities (i.e., anhedonia) is a core symptom of many psychiatric disorders, including mood and psychotic disorders (Barch et al, 2016;Lambert et al, 2018;Nusslock & Alloy, 2017). Similar motivational deficits have been recapitulated in rodent models useful for the study of depression and schizophrenia, including rodent models of early life stress (ELS) (Birnie et al, 2022; Sasha Oak and Christine Nguyen contributed equally to the published work. Duque-Quintero et al, 2022;Rincon-Cortes, 2023;Scheggi et al, 2018;Slaney et al, 2018;Young & Markou, 2015).…”

“…Duque-Quintero et al, 2022;Rincon-Cortes, 2023;Scheggi et al, 2018;Slaney et al, 2018;Young & Markou, 2015). Although sex differences in reward-related responses have been reported in adult animals following ELS (Birnie et al, 2022;Rincon-Cortes, 2023;Williams et al, 2022), less is known regarding the normative development of rewardrelated responses in both sexes. Comparing reward-related behavioral responses between developing male and female rats may be useful for understanding how these processes may be affected across early development and in rodent models relevant to psychiatric disorders.…”

“…In addition, sex differences have also been reported for social play behaviors, in which males often show increased play fighting (Pellis & Pellis, 1990; Pellis et al., 1997). Notably, sex differences in response to consummatory and social rewards have also been observed in rodent models of ELS such as maternal separation (MS) or limited bedding and nesting (LBN), which typically reduce sucrose preference/consumption in adult male rats and exert stressor‐specific effects on palatable food (i.e., MS‐induced increase in consumption in adult males and females, LBN‐induced decrease in males, increase in females) and social play (i.e., MS‐induced decrease in females, LBN‐induced decrease in males) (Birnie et al., 2022; Rincon‐Cortes, 2023). Yet, less is known about potential sex differences in response to natural rewards during early development and in normative conditions, as most studies have been conducted in adult male animals after an experimental manipulation (e.g., adversity exposure, genetic mutation, etc.)…”

Annual Research Review: The power of predictability – patterns of signals in early life shape neurodevelopment and mental health trajectories

“…In both our experimental work with rodent models and our human studies, we see growing evidence that males and females are differentially responsive to unpredictable early life experiences. In rodents, early life unpredictability differentially impacts males and females in anhedonic and reward‐seeking behaviors, with females exhibiting increased propensity for substance seeking and addiction and males evidencing increased anhedonia (Birnie, Levis, Mahler, & Baram, 2022; Levis, Baram, & Mahler, 2022; Levis, Birnie, et al., 2022; Levis, Mahler, & Baram, 2021). Further, sex‐specific patterns of responses to ELA including unpredictability are observed in CRH‐related gene expression, critically associated with stress responding and risk for psychopathology (Demaestri et al., 2022).…”