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Review
. 2025 Sep 8:19:1644383.
doi: 10.3389/fnbeh.2025.1644383. eCollection 2025.

The role of motivation in eating disorders: understanding sex differences in the circuits

Sofia Nasini #  1 , Antonino Casile #  1   2   3   4 , Brigitta Bonaldo  5 , Camilla Mancini  2 , Serafina Manila Guzzo  2   6   7 , Luca Botticelli  2 , Stefano Comai  1   8   9
Affiliations
Review

The role of motivation in eating disorders: understanding sex differences in the circuits

Sofia Nasini et al. Front Behav Neurosci. .

Abstract

Motivated behaviors, such as reproduction and feeding, are essential for mammalian survival. Although these behaviors serve distinct evolutionary purposes, they share a common function: fulfilling specific biological needs. Their regulation involves distinct brain regions and is influenced by a complex interplay of neural circuits, with significant sex-based differences. Alterations in motivation represent critical components of effort-based decision-making processes in eating disorders (EDs). Importantly, the impairments in motivated behavior observed in EDs arise not from structural changes within the relevant brain regions but rather from functional alterations influenced primarily by gonadal hormones. These hormones play a pivotal role in the pathophysiology of EDs, driving sex-based differences in both the qualitative aspects of symptom presentation and developmental trajectories through intracellular genomic signaling pathways. The current review examines sex differences in motivated behavior within the context of EDs.

Keywords: eating disorders; motivated behavior; murine models; neuronal pathways; neurotransmitters; sex differences.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Diagram of a rodent brain showing neural pathways. Solid lines represent excitatory pathways and dashed lines represent inhibitory pathways. Labeled regions include mPFC, OFC, ACC, IG, DS, NAc, LH, Hipp, Amy, and VTA.
FIGURE 1
Sagittal view of mouse brain with excitatory and inhibitory connections between neural areas. Sagittal view of the mouse brain showing the excitatory and inhibitory connections between neural areas. Schematic representation shows the excitatory and inhibitory connections among different areas that drive motivational behaviors. Inhibitory projections are indicated with a dotted line, while excitatory projections are indicated with a solid line. mPFC, medial Prefrontal cortex; OFC, orbitofrontal cortex; ACC, anterior cingulate cortex; IG, indusium griseum; DS, dorsal striatum; NAc, accumbens nucleus; LH, lateral hypothalamic area; AMY, amygdala; Hipp, hippocampus; VTA, ventral tegmental area.
Diagram illustrating brain circuitry involved in the adjustment of the reward circuit. It shows three main components: the cognitive control circuit, ventral limbic neural circuitry, and anterior insula hub, each with specific brain regions and functions like decision-making, emotional evaluation, and interoceptive cue processing. An arrow indicates the process leads to reward circuit adjustment. Below, silhouettes labeled AN and BED compare changes in brain regions: insula, lateral PFC, and medial PFC, with arrows indicating differences.
FIGURE 2
Brain areas involved in eating disorders. The representative diagram illustrates the different areas involved in the motivational circuitry, highlighting their relative functions and how they are differently altered in Anorexia Nervosa and Binge Eating Disorder. ACC, anterior cingulate cortex; AN, anorexia nervosa; BED, binge eating disorder; CPu, caudate putamen; dACC, dorsal anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; NAc, nucleus accumbens; PFC, prefrontal cortex.
Diagram of a rat brain showing neurotransmitter pathways. Dashed lines represent glutamate, solid lines represent dopamine, and dotted lines represent GABA. Key areas labeled include ACC, mPFC, OFC, CPu, NAc, VP, CeA, BLA, PVT, PVN, POA, LH, VTA, SN, PB, and IF.
FIGURE 3
Neural circuits underlying motivated “desire” and hedonic “satisfaction.” Diagram summarizing cell connections between limbic, cortical and midbrain nuclei. GABAergic projections are indicated with a dotted line, dopaminergic projections are indicated with a solid line, and glutamatergic projections are indicated with a dashed line. mPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; ACC, anterior cingulate cortex; IF, interfascicular nucleus; NAc, accumbens nucleus; CPu, caudate putamen (striatum); VP, ventral pallidum; PVN, paraventricular hypothalamus nucleus; PVT, paraventricular thalamic nucleus; POA, medial preoptic area; LH, lateral hypothalamic area; BLA, basolateral amygdaloid nucleus, anterior part; CeA, central amygdaloid nucleus, anterior part; SN, substantia nigra; VTA, ventral tegmental area; PB, parabrachial nucleus.
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