Suppression of Corticostriatal Circuit Activity Improves Cognitive Flexibility and Prevents Body Weight Loss in Activity-Based Anorexia in Rats

Milton, Laura K; Mirabella, Paul N.; Greaves, Erika; Spanswick, David; Buuse, Maarten van den; Oldfield, Brian J.; Foldi, Claire J.

doi:10.1016/j.biopsych.2020.06.022

Cited by 43 publications

(42 citation statements)

References 63 publications

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“…This may lead to an activation of the frontostriatal brain circuitry, potentially contributing to habit formation [ 27 ]. Consistent with that notion is a recent study using an animal model for AN that found that suppression of corticostriatal connections improved cognitive flexibility and was associated with less weight loss, suggesting that reducing higher-order cortical input to the subcortical reward circuitry might be beneficial to treat AN, by reducing cognitive rigidity and anxiety [ 41 ].…”

Section: Resultsmentioning

confidence: 70%

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From Desire to Dread—A Neurocircuitry Based Model for Food Avoidance in Anorexia Nervosa

Frank

2021

JCM

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Anorexia nervosa is a severe psychiatric illness associated with food avoidance. Animal models from Berridge et al. over the past decade showed that environmental ambience, pleasant or fear inducing, can trigger either appetitive (desire) or avoidance (dread) behaviors in animals via frontal cortex, nucleus accumbens dopamine D1 and D2 receptors, and hypothalamus. Those mechanisms could be relevant for understanding anorexia nervosa. However, models that translate animal research to explain the psychopathology of anorexia nervosa are sparse. This article reviews animal and human research to find evidence for whether this model can explain food avoidance behaviors in anorexia nervosa. Research on anorexia nervosa suggests fear conditioning to food, activation of the corticostriatal brain circuitry, sensitization of ventral striatal dopamine response, and alterations in hypothalamic function. The results support the applicability of the animal neurocircuitry derived model and provide directions to further study the pathophysiology that underlies anorexia nervosa.

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Section: Resultsmentioning

confidence: 70%

“…A biological approach could apply in humans where “turning off” of frontal input was able to improve survival in the ABA model [ 41 ]. In fact, a recent pilot study in AN using repetitive transcranial magnetic stimulation found less over-control for food choices, suggesting more cognitive flexibility [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

From Desire to Dread—A Neurocircuitry Based Model for Food Avoidance in Anorexia Nervosa

Frank

2021

JCM

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“…Studies have emphasized the behavioral complexities of ABA, and more recent reports have begun to unravel the neurobiology potentially underlying ABA 34,42,[45][46][47]56,57 . Despite these advances, no study to date has identified a neural circuit capable of combating ABA development and/or progression by addressing both anorexia and hyperactivity.…”

Section: Discussionmentioning

confidence: 99%

AgRP neurons coordinate the mitigation of activity-based anorexia

Sutton

Duane

Shamma

et al. 2021

Preprint

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Anorexia nervosa (AN) is a debilitating and deadly disease characterized by low body mass index due to diminished food intake, and oftentimes concurrent hyperactivity. A high percentage of AN behavioral and metabolic phenotypes can be replicated in rodents given access to a voluntary running wheel and subject to food restriction, termed activity-based anorexia (ABA). Despite the well-documented body weight loss observed in AN human patients and ABA rodents, much less is understood regarding the neurobiological underpinnings of these maladaptive behaviors. Moreover, while exercise has been shown to diminish the activity of hunger-promoting hypothalamic agouti-related peptide (AgRP) neurons, much less is known regarding their activity and function in the mediation of food intake during ABA. Here, feeding microstructure analysis revealed ABA mice decreased food intake due to increased interpellet interval retrieval and diminished meal number. Longitudinal activity recordings of AgRP neurons in ABA animals revealed a maladaptive inhibitory response to food. We then demonstrated that ABA development or progression can be mitigated by chemogenetic AgRP activation through the reprioritization of food intake (increased meal number) over hyperactivity. These results elucidate a potential neural target for the amelioration of behavioral maladaptations present in AN patients.

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“…Indeed, the mPFC-LH circuit may play important and underappreciated roles in the pathogenesis of psychometabolic conditions at opposite ends of the body weight sprectrum. For example, excessive cognitive control related to increased mPFC activity is associated with anorexia nervosa 11 and excessive dietary self control 6 , while chronic inhibiton of the mPFC reduces anorectic symptoms in a rat model of activity-based anorexia 70 . On the other hand, decreased activity upon consumption removes this restraint and may, in some circumstances, promote body weight gain.…”

Section: Discussionmentioning

confidence: 99%

Identification of a stress-sensitive anorexigenic neurocircuit from medial prefrontal cortex to lateral hypothalamus

Clarke

Voigt

Stark

et al. 2021

Preprint

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Animal models that examine neural circuits controlling food intake often lack translational relevance. To address this limitation, we identified neural network dynamics related to homeostatic state and BMI in humans. This approach predicted a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans. We then dissected the mechanistic underpinnings of this human-relevant mPFC-LH circuit in mice. Chemogenetic or optogenetic activation of the mPFC-LH pathway in mice suppressed food intake and motivated sucrose-seeking. Fibre photometry demonstrated this pathway was active in response to acute stress or prior to novel environment or object exposure, suggesting a role in the predictive assessment of potential threat. Food consumption suppressed mPFC-LH neuronal activity, independent of metabolic state or palatability. Finally, inhibition of this circuit increased feeding and motivated behaviour under mild stress and chronic ablation caused weight gain. These studies identify the mPFC-LH as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake and motivated reward-seeking.

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Suppression of Corticostriatal Circuit Activity Improves Cognitive Flexibility and Prevents Body Weight Loss in Activity-Based Anorexia in Rats

Cited by 43 publications

References 63 publications

From Desire to Dread—A Neurocircuitry Based Model for Food Avoidance in Anorexia Nervosa

From Desire to Dread—A Neurocircuitry Based Model for Food Avoidance in Anorexia Nervosa

AgRP neurons coordinate the mitigation of activity-based anorexia

Identification of a stress-sensitive anorexigenic neurocircuit from medial prefrontal cortex to lateral hypothalamus

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