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Toward understanding dopamine receptor contributions to prediction error and reversal learning in anorexia nervosa

了解多巴胺受体对神经性厌食症预测误差和逆转学习的贡献

基本信息

批准号：
9805065
负责人：
Guido KW Frank
金额：
$ 23.63万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9805065
关键词：
Adolescent Adult Agonist American Psychiatric Association Amisulpride Anorexia Nervosa Avoidance Learning Behavioral Biological Markers Body Weight decreased Brain Brain imaging Bromocriptine Clinical Research Code Control Groups Corpus striatum structure Data Development Disease Dopamine Dopamine D1 Receptor Dopamine D2 Receptor Dopamine Receptor Eating Eating Disorders Exploratory/Developmental Grant Food Foundations Fright Functional disorder Funding Mechanisms Future Human Impairment Individual Insula of Reil Intervention Investigation Magnetic Resonance Mental disorders Neurotransmitter Receptor Neurotransmitters Pathway interactions Pharmaceutical Preparations Pharmacological Treatment Pharmacology Phase Placebos Population Protocols documentation Relapse Research Research Design Reversal Learning Rewards Role Serotonin Signal Transduction Stimulus Taste Perception Testing Ventral Striatum Weight Gain Woman aripiprazole behavioral response brain behavior dopamine system dopaminergic neuron effective therapy food restriction frontal lobe improved learned behavior mortality neuroimaging psychologic receptor response reward circuitry reward processing

项目摘要

Project Summary/Abstract Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known about biomarkers, and no medication has been approved for AN. Many individuals only partially recover, and treatment options, especially for the psychological components of the illness, are not very effective, highlighting the need for more effective treatments. Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have suggested altered reward processing in AN. The neurotransmitter dopamine has a central role in the reward circuitry to drive food approach, and the dynamic interplay between dopamine receptor response and food restriction could have implications for the pathophysiology of AN. Dopamine-related brain function has been studied indirectly using functional magnetic resonance brain imaging (fMRI) and tasks that deliver reward stimuli unexpectedly, eliciting the so-called prediction error (PE) response. Research in AN showed repeatedly altered PE processing suggesting altered dopamine circuit function in the disorder. Dopamine and PE response have also been associated with altered reversal learning, which has important treatment implication for AN as reversal learning is impaired in the disorder and modulation of the dopamine system could improve treatment. However, the dopamine receptor mechanisms that underlie altered PE response in AN have not been studied. This could be highly important to develop medication interventions. In this application, we will develop a study protocol and gather pilot data to identify whether specific dopamine D2 challenge drugs can modulate PE response and reversal learning in AN. In Aim 1., we will apply a selective dopamine D2 receptor agonist to test its effects on PE and reversal learning. In Aim 2., we will apply a selective dopamine D2/3 receptor antagonist. We expect that those challenge drugs will lead to opposite brain and behavior response within groups and directly support the involvement of those receptors in PE and reversal learning processing. In Aim 3., we will contrast brain and behavior response across challenge drugs in AN against response in healthy controls to gather pilot data for future investigation. This research will be important to develop neurotransmitter specific pharmacological treatments for AN.

项目总结/文摘