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Early experience and neurobiological risks of adult cocaine use disorder

Award Number: R01DA052909
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Early experience and neurobiological risks of adult cocaine use disorder - Abstract This competing renewal continues the longitudinal study of long-term effects of early life stress (ELS) caused by infant maltreatment (MALT) on reward and stress/emotional regulation of adult macaques. We have identified behavioral phenotypes (anxiety/impaired emotional regulation) and neural biomarkers of risk for cocaine self-administration (COC SA). During the prior funding period we focused on functional connectivity (FC), dopamine (DA) and serotonin (5-HT) receptor function, and changes/adaptations in response to prolonged COC intake beginning in adolescence and continuing into adulthood. Adolescence initiation of drug use is a main risk factor for lifelong addiction, although the neurobiological factors associated with vulnerability to substance use disorders (SUDs), including COC use disorder (CUD), are poorly understood. We have been studying how ELS followed by COC use during adolescence results in long-term alterations in brain circuits critical for stress/emotional regulation and reward, behavior (anxiety) and on subsequent cocaine use. Our unique cohort of female and male rhesus monkeys characterized from birth through adulthood allows for the identification of early life risk factors and neurobiological mechanisms of individual variability in vulnerability to adult CUD and lifelong substance misuse, including relapse following abstinence. Our hypothesis is that there are different underlying “neurobiological signatures” shaped by ELS and adolescence COC exposure that lead to different underlying behavioral and cognitive “drives” (e.g., anxiety) that contribute to risk for SUDs in adults. The goal is to identify the underlying neurobiological mechanisms of individual variability in risk to COC choice in adulthood and differential treatment efficacy. Aim 1 will examine behavioral and stress phenotypes and their neurobiological signatures as predictors of COC choice. Aim 2 will examine the influence of ELS, adolescence cocaine history and sex on the effects of behavioral and pharmacological interventions on COC vs. food choice in adult macaques. And Aim 3 will determine the role of amygdala and medial prefrontal cortex (mPFC) circuits projecting to the nucleus Accumbens on COC choice using circuit-specific chemogenetics.


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 = $881,232 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	002	6	9/4/2026	COMPETING CONTINUATION	$881,232
2026	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	001	5	8/27/2026	NON-COMPETING CONTINUATION	$0
2026	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	000	5	11/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $881,232

Issue Date FY: 2025 ( Subtotal = $723,418 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	001	5	4/10/2025	NON-COMPETING CONTINUATION	$72,340
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	000	5	1/24/2025	NON-COMPETING CONTINUATION	$651,078
														Subtotal = $723,418

Issue Date FY: 2024 ( Subtotal = $806,311 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	000	4	1/26/2024	NON-COMPETING CONTINUATION	$725,682
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	001	4	4/25/2024	NON-COMPETING CONTINUATION	$80,629
														Subtotal = $806,311

Issue Date FY: 2023 ( Subtotal = $808,680 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	000	3	1/26/2023	NON-COMPETING CONTINUATION	$808,680
														Subtotal = $808,680

Issue Date FY: 2022 ( Subtotal = $808,119 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	000	2	1/18/2022	NON-COMPETING CONTINUATION	$727,308
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	001	2	3/18/2022	NON-COMPETING CONTINUATION	$80,811
														Subtotal = $808,119

Issue Date FY: 2021 ( Subtotal = $827,551 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Drug Use and Addiction Research Programs	000	1	3/30/2021	NEW	$827,551
														Subtotal = $827,551

Grand Total All Awards = $4,855,311

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Early experience and neurobiological risks of adult cocaine use disorder

Award Number: R01DA052909

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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