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

Award Number: R21MH120475
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	2	1/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	2	8/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $196,875 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	2	5/1/2020	NON-COMPETING CONTINUATION	$196,875
2020	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	4/29/2020	NEW	$0
														Subtotal = $196,875

Issue Date FY: 2019 ( Subtotal = $236,250 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	7/31/2019	NEW	$236,250
														Subtotal = $236,250

Grand Total All Awards = $433,125

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

Award Number: R21MH120475

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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