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Neural mechanisms of motivational and cognitive impairment in opioid withdrawal

Award Number: R01DA064341
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2025
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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Neural mechanisms of motivational and cognitive impairment in opioid withdrawal - Summary The opiate epidemic has led to a surge in overdose deaths and significant societal and economic costs. Opiate withdrawal poses obstacles to recovery by causing emotional, motivational, and cognitive disturbances that disrupt one’s ability to pursue adaptive goals. Understanding the neural mechanisms underlying these withdrawal-induced deficits may facilitate strategies to promote abstinence. Our preliminary research shows that rats experiencing acute morphine withdrawal exhibit reduced motivation and impaired cognitive, goal-directed control over their actions. This project will test the innovative hypothesis that opioid withdrawal-induced motivational deficits are mediated by opposing adaptations in dopamine (DA) and acetylcholine (ACh) release in the nucleus accumbens (NAc) and that withdrawal-induced deficits in goal-directed action selection result from aberrant DA and ACh signaling in the dorsomedial striatum (DMS). We will also investigate whether dysregulated D1- and D2-striatal projection neuron (SPN) activity in the NAc and DMS contributes to withdrawal-induced deficits in motivation and action selection, respectively. Aim 1 will combine sophisticated behavioral analysis, quantitative no-net-flux microdialysis, and fiber photometry to determine the impact of acute and protracted morphine withdrawal on tonic and phasic DA and ACh release and D1/D2 SPN calcium activity in the NAc and DMS, and how these effects relate to deficits in motivation and action selection. Aim 2 will test whether these behavioral deficits can be ameliorated, exacerbated, and mimicked through cell-type and region-specific chemogenetic and optogenetic manipulations of striatal DA and ACh release and D1/D2 SPN activity. The study aims to uncover novel neurochemical and neurocircuit mechanisms contributing to anhedonia-like symptoms in morphine withdrawal, guiding future strategies to combat opioid use disorder.


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: 2026 ( Subtotal = $665,240 )
2026	2026	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Drug Use and Addiction Research Programs	000	2	5/27/2026	NON-COMPETING CONTINUATION	$665,240
														Subtotal = $665,240

Issue Date FY: 2025 ( Subtotal = $650,250 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Drug Use and Addiction Research Programs	001	1	9/18/2025	NEW	$0
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Drug Use and Addiction Research Programs	000	1	8/29/2025	NEW	$650,250
														Subtotal = $650,250

Grand Total All Awards = $1,315,490

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Neural mechanisms of motivational and cognitive impairment in opioid withdrawal

Award Number: R01DA064341

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2025

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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