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Neural signals controlling generalized deficits in motivation

Award Number: R21MH133062
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/15/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Neural signals controlling generalized deficits in motivation - Generalized deficits in motivation and impaired reward-seeking are behavioral symptoms associated with mental health disorders. Identifying the neural signals responsible for generalized deficits in motivation requires a task capable of examining the motivation to work for multiple reward options. While common motivation assays can track a reduction in effort when a reward is decreased in size, these assays typically offer a single reward option and cannot be used to study generalized deficits in motivation in a single setting. To overcome this limitation, the lab developed a novel rodent task that simultaneously assesses the motivation to work for two distinct rewards. In this task the effort required to earn a reward increases across trials under a progressive ratio (PR) reinforcement schedule (Concurrent PR task). Importantly, the PR schedules for both reward options are independent of one another. Rats were exposed to test sessions where one of the reward options was decreased in size. Rats were categorized based on their reward seeking strategy during tests sessions to examine how the net yield of rewards is impacted by changes in motivation. Reward ‘maximizers’ earned the same/more rewards than would be expected whereas reward ‘non-maximizers’ earned fewer rewards than would be expected. Preliminary data illustrate that ‘non-maximizers’ decrease the motivation to work for both reward options. The goal of this proposal is to (1) identify the neural signals responsible for generalized motivational deficits in rats employing a ‘non-maximizer’ strategy and (2) implement rational strategies to reverse these motivation impairments. Altered dopamine signaling in the nucleus accumbens core (NAc) could mediate these generalized deficits in motivation since NAc dopamine facilities high-effort actions and contributes to value-based decision-making. In preliminary studies we recorded NAc dopamine in rats trained on the Concurrent PR task. During test sessions when one reward was decreased in size, ‘non-maximizers’ exhibited smaller dopamine responses to both reward options relative to ‘maximizers’. The phenomenon could be explained by (1) the dopamine system in ‘non-maximizers’ reflecting changes in the average reward size at a faster rate relative to ‘maximizers’ or (2) ‘non-maximizers’ having an intrinsically smaller reward-evoked dopamine response relative to ‘maximizers’. In this proposal, NAc dopamine release will be recorded to determine which model (difference in updating reward value vs intrinsic difference) accounts for the dampened reward-evoked dopamine response in ‘non- maximizers’ (Aim 1). These findings will inform the predictions in Aim 2, where optogenetic manipulations of reward-evoked dopamine release will be performed to identify rational strategies to reverse generalized deficits in motivation.


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: 2025 ( Subtotal = $217,500 )
2025	2025	THE UNIVERSITY OF TEXAS AT SAN ANTONIO	1 UTSA CIR	SAN ANTONIO	TX	78249	BEXAR	USA	Mental Health Research Grants	000	2	11/19/2024	NON-COMPETING CONTINUATION	$184,875
2025	2025	THE UNIVERSITY OF TEXAS AT SAN ANTONIO	1 UTSA CIR	SAN ANTONIO	TX	78249	BEXAR	USA	Mental Health Research Grants	001	2	9/22/2025	NON-COMPETING CONTINUATION	$32,625
														Subtotal = $217,500

Issue Date FY: 2024 ( Subtotal = $180,000 )
2024	2024	UNIVERSITY OF TEXAS AT SAN ANTONIO, THE	1 UTSA CIRCLE	SAN ANTONIO	TX	78249	BEXAR	USA	Mental Health Research Grants	000	1	11/14/2023	NEW	$180,000
														Subtotal = $180,000

Grand Total All Awards = $397,500

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Neural signals controlling generalized deficits in motivation

Award Number: R21MH133062

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 11/15/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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