Understanding how motivated behaviors become dysfunctional is essential for elucidating the pathophysiology of psychiatric disorders, including EDs. Motivation refers to goal-directed behaviors aimed at achieving rewarding outcomes that satisfy essential needs. Although eating is vital for survival, its disruption may indicate underlying neurobiological alterations.

The mesocorticolimbic system, which includes the ventral tegmental area (VTA), NAc, limbic regions, and PFC, plays a central role in rewards processing and motivation (Kelley and Berridge, 2002; Robbins and Everitt, 2007). Within this circuitry, dopamine (DA) modulates rewards anticipation, reinforcement learning, and incentive salience (Eck and Bangasser, 2020). DA release in the NAc supports goal-directed actions, while DA activity in the striatum is associated with rewards consumption (Baldo et al., 2013; Small et al., 2003).

Compulsive and maladaptive behaviors, such as those seen in EDs, are linked to dysregulated DA signaling, particularly between the dorsolateral PFC and NAc (Ampel et al., 2016). Impaired self-control and altered rewards processing may thus contribute to pathological eating behaviors, reinforcing the relevance of dopaminergic circuits in EDs vulnerability (Leigh and Morris, 2018; Volkow et al., 2013).

Eating is a motivated behavior essential for survival (Blundell and Rogers, 1991). According to the homeostatic feedback theory, food intake is regulated by physiological and behavioral mechanisms involving motivational systems. Cognitive processes, including hunger and satiety, are controlled by peripheral signals (e.g., ghrelin, leptin, insulin, cortisol) informing the central nervous system (CNS) about the body’s energy status. These signals trigger behaviors designed to regulate food-seeking and intake (Cosmides and Tooby, 2013; Deckers, 2018). Key brain regions involved, such as the PFC, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC), manage inhibitory and excitatory balance, crucial for processing rewarding stimuli and regulating emotional responses, especially in BN (Ikemoto, 2010; Kelley and Berridge, 2002; Robbins and Everitt, 2007; Figure 1).

Neuroplastic changes within these regions, influenced by both genetic predispositions and environmental factors such as stress, contribute to the development and maintenance of disordered eating behaviors (Bonaldo et al., 2024; Brewerton, 2015; Micioni Di Bonaventura et al., 2014). The brain’s rewards system comprises ventral and dorsal circuits: the ventral limbic system, including the anterior insula, ventral striatum, amygdala, OFC, and ACC, is responsible for recognizing rewarding stimuli and emotional responses, while the dorsal circuit, involving dorsal striatum, parietal cortex, and DLPFC, manages planning, regulation, and selective attention (Phillips et al., 2003). Dysfunction in these circuits, particularly in rewards processing and food intake regulation, contributes to maladaptive behaviors observed in EDs, such as BED and restrictive eating (Lee et al., 2017; Marazziti and Catena Dell’osso, 2008; Wang et al., 2023).

Clinically, AN, BN, and BED suggest dysregulation of motivational and rewards systems. In AN, reduced gratification from food restriction, and in BED, excessive food consumption to mitigate negative emotions, significantly contributes to the initiation and maintenance of these disorders (Monteleone et al., 2018). Such behaviors reflect underlying alterations in cognitive and motivational circuits regulated by neurotransmitters like DA, serotonin (5-HT), and neuropeptides (Bromberg-Martin et al., 2010; Johnson and Kenny, 2010).

Research indicates motivational changes in EDs result from intrinsic biological processes and environmental influences. For instance, a key symptom in EDs is anhedonia, a diminished ability to experience gratification linked to alter DA system. Food restriction, typical of AN, sensitizes DA pathways, whereas excessive food consumption in BED desensitizes these pathways, due to decreased DA receptor (DR) expression (Carr et al., 2003). These DA system alterations affect cognitive and motivational circuits, modulated by peripheral signals like leptin, ghrelin, glutamate, and opioids (Carr et al., 2010; Koizumi et al., 2009; Opland et al., 2010; Perello et al., 2010).

In AN, caloric restriction elevates DA release, promoting excessive physical activity as reward-seeking behavior. This heightened activity reinforces restrictive behaviors through 5-HT-mediated satiety signaling (Kaye et al., 2009; Keating et al., 2012). Conversely, recurrent binge-eating episodes in BED show neurobiological parallels with substance addiction, featuring functional abnormalities in neurotransmitter systems (DA, opioids) and impaired frontostriatal circuitry, underpinning impulsiveness and rewards craving (Novelle and Dieguez, 2018).

Therefore, eating behavior intricately involves motivational pathways modulated by genetic, hormonal, and environmental factors. Understanding these dysregulated motivational circuits provides insight into the neurobiological and psychological underpinnings of EDs.

These two circuits work together to evaluate environmental stimuli, associate them with rewards, and assess future consequences (Goldstein and Volkow, 2011).

Disruptions in these circuits, particularly in rewards processing and regulation of food intake, can lead to maladaptive behaviors such as binge eating or restrictive behaviors characteristic of EDs (Monteleone et al., 2018).

The clinical features of AN, BN, and BED suggest that EDs may stem from dysregulation of the motivational or rewards systems. The diminished sense of gratification from food restriction, and the excessive consumption of food to alleviate negative emotions observed in AN and BED, respectively, both contribute to the initiation and maintenance of harmful behaviors, which are closely related to alterations in cognitive functions that regulate eating behavior (de Souza et al., 2018).

Further research has indicated that these motivational changes are not solely due to external factors but may also be influenced by intrinsic biological processes, including altered signaling of key neurotransmitters.

A key symptom in EDs is anhedonia, which is the reduced ability to experience gratification. This alteration impacts one of the primary rewards circuits, specifically the VTA. When rewarding stimuli are perceived, DA is released from the VTA, triggering a cascade of brain responses: it stimulates the NAc, promotes associative learning via the hippocampus, and processes emotions through the amygdala. The integration of these responses facilitates behaviors related to reward-seeking and learning. Research has shown that individuals with EDs exhibit altered DA systems, leading to changes in cognitive functions associated with rewards and motivation (Monteleone et al., 2018; Figure 2).

Food restriction, common in AN, has been linked to increased sensitization of DA pathways in rewards circuits (Carr et al., 2003). Conversely, the excessive food consumption characteristic of BED leads to desensitization of these circuits, caused by reduced expression of DRs (Johnson and Kenny, 2010). These changes in body weight are associated with impairments in both cognitive and motivational circuits, affecting DA signaling pathways. Moreover, altered production of leptin (Opland et al., 2010), ghrelin (Perello et al., 2010), glutamate (Carr et al., 2010), and opioids (Koizumi et al., 2009) further disrupt the rewards system.

Increased body weight, particularly in the case of BED, has been shown to negatively impact the regulation of DRs sensitivity, leading to dysregulated feeding behaviors.

Changes in body weight also correlate with impairments in neural circuits involved in motivation. In AN, alterations in neuropeptides related to appetite, the hypothalamic-pituitary-adrenal (HPA) axis, 5-HT, and DA pathways are observed (Kaye, 2008; Sodersten et al., 2008). Caloric restriction in AN triggers an increase in DA release, which in turn promotes exercise as a reward-seeking behavior. This increased motor activity provides a sense of fulfillment through the release of 5-HT, which in turn promotes satiety and reduces food intake (Kaye et al., 2009). The excessive release of neurotransmitters in AN alters motivational circuits and, as a result, emotional perception and the sense of fulfillment (Keating et al., 2012).

Recurrent binge eating episodes in BED share similarities with behaviors seen in substance dependence (Novelle and Dieguez, 2018). Functional abnormalities in neurotransmitter systems (e.g., DA and opioids) and frontostriatal changes are key characteristics of BED, such as loss of control over impulsiveness and the craving for rewarding stimuli. These symptoms reflect underlying alterations in motivational circuits (Novelle and Dieguez, 2018).

As with other addictive behaviors, the loss of control in BED may be attributed to alterations in the reinforcement learning pathways, which are critical in driving behaviors related to food intake and emotional regulation (Monteleone et al., 2018).

In conclusion, eating behavior is intricately linked to motivation and regulated by both peripheral and central signaling pathways. EDs disrupt these pathways, leading to significant alterations in rewards systems. These disruptions affect how individuals with EDs perceive and process emotional states, rewards, and gratification (Monteleone et al., 2018).

Given the role of motivation in eating behavior, it follows that disruptions in motivational circuits are central to EDs pathology. Understanding how these circuits become dysregulated can provide insights into both the neurobiological and psychological aspects of EDs.

As previously discussed, motivation and other behaviors exhibit sex differences that depend on genetic predispositions, hormonal influences, and environmental contexts. Gonadal hormones are particularly critical, exerting both organizational effects, permanent alterations occurring early in development, and activational effects, which are temporary and hormone-dependent changes throughout life (Arnold and Breedlove, 1985; Blencowe et al., 2022).

Importantly, these hormonal effects influence functional neural activity rather than gross anatomical structures, shaping sex differences in brain regions implicated in motivation.

Despite complexity in the underlying mechanisms, sex-related regions involved in emotional and cognitive processing contribute substantially to motivated behaviors (Eck and Bangasser, 2020). To elucidate how sex differences shape motivation, we examine the anatomical organization of the neural circuits underlying reward-related behaviors, with particular attention to sex-specific features and hormonal influences.

In addition to the mesocorticolimbic rewards circuitry described above, motivated behaviors are strongly influenced by emotional processes. Emotional regulation involves key limbic areas such as BNST and the amygdala. These regions show marked sex-based differences in animal models, which could help explain the observed disparities between males and females in susceptibility to EDs.

In humans, EDs emerge from a multifactorial interplay between biological predispositions and non-biological influences. Sociocultural norms, environmental exposures, and psychosocial stressors critically shape the onset, trajectory, and clinical expression of these complex conditions. In parallel, epigenetic mechanisms, responsive to early-life experiences, nutritional status, and chronic stress, may induce persistent changes in gene expression, thereby influencing neural circuits involved in motivation, emotion regulation, and rewards processing. Importantly, these environmental and epigenetic factors may interact with sex-specific hormonal and neurobiological substrates, ultimately contributing to individual variability in symptom presentation, disease severity, and treatment response. To advance our understanding of EDs pathophysiology, it is critical to bridge preclinical insights with human studies. Integrating findings from animal models with neuroimaging, genetic, and epigenetic research in clinical populations could accelerate the identification of novel biomarkers and therapeutic targets, while increasing our knowledge of the underlying neurobiology. Recognizing sex as a fundamental biological variable in both basic and translational research is essential for the development of personalized and more effective interventions. Future research should prioritize longitudinal and interdisciplinary approaches that account for sex differences, hormonal status, and environmental exposures to better elucidate the complex and dynamic neurobiology underlying EDs.