Dissecting corticostriatal circuitry underlying chronic binge eating
剖析慢性暴饮暴食背后的皮质纹状体回路
基本信息
- 批准号:10226723
- 负责人:
- 金额:$ 3.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAnorexia NervosaAreaBRAIN initiativeBehaviorBehavior DisordersBehavioral ParadigmBinge EatingBinge eating disorderBiological PharmacologyBrainBulimiaChronicColorCompulsive BehaviorConsumptionControl GroupsCorpus striatum structureDependenceDevelopmentDiagnosisDiagnosticDisease modelEatingEating BehaviorEating DisordersEquilibriumEtiologyEvolutionExtinction (Psychology)FeelingFeeling suicidalFiberFoodFunctional disorderGoalsHabitsHumanInterventionLeadLinkLithium ChlorideMaintenanceMediatingMedicalMental HealthMental disordersMethodsModelingMusNational Research Service AwardsNeuronsNeurosciencesNon-Insulin-Dependent Diabetes MellitusObesityObsessive-Compulsive DisorderOutcomePalatePathway interactionsPatternPharmacological TreatmentPharmacologyPhotometryPhysiologicalRattusResearchResistanceStructureSubstance Use DisorderTechniquesTestingTherapeutic InterventionTimeTrainingcostdesigner receptors exclusively activated by designer drugsdisability burdeneffective therapyflexibilityin vivoinsightmortalitymouse modelneural circuitoptogeneticspre-doctoralpsychologicpsychosocialrelating to nervous systemrepetitive behaviorsevere mental illnesssevere psychiatric disorder
项目摘要
ABSTRACT
Eating disorders are severe psychiatric conditions with a significant worldwide cost and disability burden. Binge
eating (BE) is a behavior that cuts across nearly all eating disorder diagnoses. Unfortunately, psychological
treatments for eating disorders/BE are limited, and targeted biological/pharmacological treatments have not yet
been effective. In order to develop more effective targeted treatments, it is critical to understand the neural
circuit abnormalities that contribute to the onset, expression, and maintenance of BE. Specifically, studies
targeting the neural underpinnings of chronic and repetitive BE will substantially deepen our understanding of
the behavior. Other severe psychiatric conditions involving repetitive behaviors (e.g., obsessive compulsive
disorder [OCD], substance use disorders) are associated with differences in neural activity within corticostriatal
circuitry. Recent models of these disorders have highlighted dysfunction in the balance between goal-directed
and habitual behavior, suggesting more reliance on habit related pathways with more chronic duration of
illness. However, whether overreliance on habit related circuitry exists in chronic stages of BE, compared to
more goal-directed/habitual flexibility at acute stages of BE, has yet to be investigated. The central hypotheses
of this project are that BE is associated with 1) increased neural activity in pathways associated with goal-
directed behavior (prelimbic cortex [PL], dorsomedial striatum [DMS], PLàDMS projections) at acute stages of
BE; and 2) increased activity in structures associated with habit (infralimbic cortex [IL], dorsolateral striatum
[DLS]) as BE becomes more chronic, suggesting an evolution from dependence on goal-directed to habitual
circuits in BE over time. In order to dissect circuitry underlying BE, a mouse model of binge-like eating will be
used. Behavioral paradigms will characterize the propensity to use goal-directed and habitual behavior by
examining differences in rates of habitual responding to palatable food using lithium chloride devaluation (Aim
1a) and outcome devaluation (Aim 1b) across duration of BE. The impact of optogenetic inhibition of the IL
during outcome devaluation (Aim 1b) will also be assessed. In addition, dual color in vivo fiber photometry will
be used to quantify neural activity patterns in goal-directed and habit related networks during the development
of BE (Aim 2). In this Aim, neural activity will also be time-locked to specific BE related behaviors that are
translatable to human BE (e.g., approach, consumption), which may provide information regarding optimal
specific behaviors for therapeutic intervention. Finally, inhibitory designer receptors exclusively activated by
designer drugs (DREADDs) will be used to determine if habit related circuitry is necessary for the maintenance
of chronic BE (Aim 3). Together, the Aims proposed in this study will lead to a dramatic increase our
understanding of neural circuit function underlying BE, which could lead to more specific and targeted
treatments for this chronic and severe behavior.
摘要
项目成果
期刊论文数量(0)
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Britny Hildebrandt其他文献
Britny Hildebrandt的其他文献
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{{ truncateString('Britny Hildebrandt', 18)}}的其他基金
Dissecting circuits underlying loss of control relevant to binge eating
剖析与暴饮暴食相关的失控回路
- 批准号:
10722697 - 财政年份:2023
- 资助金额:
$ 3.32万 - 项目类别:
Dissecting corticostriatal circuitry underlying chronic binge eating
剖析慢性暴饮暴食背后的皮质纹状体回路
- 批准号:
9795363 - 财政年份:2018
- 资助金额:
$ 3.32万 - 项目类别:
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