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Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys

Award Number: R01DA017763
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2001
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys - There is an estimated 5.7 million Americans that are current cocaine users and, at present, there are no FDA- approved treatments for cocaine use disorders. This research project is a continuation of funded work aimed at understanding the behavioral, pharmacological and neurobiological variables influencing the reinforcing effects of cocaine in a unique nonhuman primate model: intravenous cocaine self-administration (SA) in socially housed cynomolgus monkeys. The goals of the present application are to continue using this homologous animal model to examine the mechanisms of action mediating the interactions between social hierarchy and environmental and pharmacological modulation of cocaine self-administration in female and male monkeys. Using PET imaging, over the previous funding period, we have noted sex- and social-rank related differences in dopamine (DA) D2/D3 receptor (D2/D3R) and kappa opioid receptor (KOR) availability in cocaine-naïve monkeys through long-term cocaine SA. Consistent with these sex- and social-rank differences, we noted individual differences in response to several pharmacological manipulations. In Aim 1, we propose to extend the characterization of sex- and social-rank differences in cocaine SA to examine several behavioral interventions. For these studies, monkeys will choose between cocaine and food and the following interventions will be examined: delay discounting involving both food and cocaine delays; changes in the magnitude of the food reinforcer, to better model contingency management; and punishment, using a KOR agonist (positive punishment), which will be important since we have measures of KOR availability in these monkeys, as well as using response-contingent timeouts (negative punishment). The studies in Aim 2 will examine the effects of chronic drug treatments in socially housed monkeys self-administering cocaine in the context of an alternative, non-drug, reinforcer (food-cocaine choice). We will also combine chronic pharmacological treatments with behavioral interventions in an effort to further decrease cocaine choice. Importantly, cognitive performance will be assessed to better determine if the intervention has unwanted side effects. The goals of Aim 3 are to examine how cocaine SA and chronic drug treatment differentially affects D2/D3R and KOR availability, using a within-subjects design, in socially housed female and male monkeys. The scientific premise is that different mechanisms maintain cocaine SA based on social rank and sex and thus different intervention strategies (both behavioral and pharmacological) will be required to produce a positive outcome in these groups. We are proposing a preclinical personalized-medicine strategy for treating cocaine abuse that incorporates sex and social variables.


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 = $683,838 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	002	17	6/20/2025	NON-COMPETING CONTINUATION	$683,838
2025	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	16	4/2/2025	COMPETING CONTINUATION	$2,847
2025	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	15	4/2/2025	SUPPLEMENT FOR EXPANSION	-$2,847
														Subtotal = $683,838

Issue Date FY: 2024 ( Subtotal = $697,498 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	16	9/6/2024	COMPETING CONTINUATION	$697,498
														Subtotal = $697,498

Issue Date FY: 2023 ( Subtotal = $122,442 )
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	15	9/6/2023	SUPPLEMENT FOR EXPANSION	$122,442
2023	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	15	9/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $122,442

Issue Date FY: 2022 ( Subtotal = $733,121 )
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	15	7/20/2022	NON-COMPETING CONTINUATION	$733,121
														Subtotal = $733,121

Issue Date FY: 2021 ( Subtotal = $836,059 )
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	14	7/21/2021	NON-COMPETING CONTINUATION	$736,213
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	13	5/3/2021	SUPPLEMENT FOR EXPANSION	$99,846
														Subtotal = $836,059

Issue Date FY: 2020 ( Subtotal = $736,217 )
2020	2020	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	13	7/29/2020	NON-COMPETING CONTINUATION	$736,217
														Subtotal = $736,217

Issue Date FY: 2019 ( Subtotal = $812,878 )
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	12	7/25/2019	SUPPLEMENT FOR EXPANSION	$76,699
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	12	7/24/2019	NON-COMPETING CONTINUATION	$736,179
2019	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	003	11	7/29/2019	COMPETING CONTINUATION	$1,878
2019	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	002	10	7/29/2019	EXTENSION WITH OR WITHOUT FUNDS	-$1,878
														Subtotal = $812,878

Issue Date FY: 2018 ( Subtotal = $735,577 )
2018	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	002	11	9/20/2018	COMPETING CONTINUATION	$735,577
2018	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	10	9/13/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
2018	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	10	2/22/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $735,577

Issue Date FY: 2016 ( Subtotal = $412,884 )
2016	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	10	3/14/2016	EXTENSION WITH OR WITHOUT FUNDS	$37,536
2016	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	10	12/10/2015	EXTENSION WITH OR WITHOUT FUNDS	$375,348
														Subtotal = $412,884

Issue Date FY: 2015 ( Subtotal = $410,799 )
2015	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	9	1/20/2015	NON-COMPETING CONTINUATION	$375,348
2015	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	9	2/10/2015	NON-COMPETING CONTINUATION	$35,451
														Subtotal = $410,799

Issue Date FY: 2014 ( Subtotal = $447,875 )
2014	2014	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	002	8	8/29/2014	SUPPLEMENT FOR EXPANSION	$30,820
2014	2014	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	8	3/3/2014	NON-COMPETING CONTINUATION	$41,705
2014	2014	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	8	12/31/2013	NON-COMPETING CONTINUATION	$375,350
														Subtotal = $447,875

Issue Date FY: 2013 ( Subtotal = $400,373 )
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	7	5/16/2013	NON-COMPETING CONTINUATION	$25,023
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	7	11/16/2012	NON-COMPETING CONTINUATION	$375,350
														Subtotal = $400,373

Issue Date FY: 2012 ( Subtotal = $372,105 )
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	6	2/21/2012	COMPETING CONTINUATION	$372,105
2012	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	5	2/21/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $372,105

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	5	5/27/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	5	4/26/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $333,356 )
2008	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	5	4/30/2008	NON-COMPETING CONTINUATION	$333,356
														Subtotal = $333,356

Issue Date FY: 2007 ( Subtotal = $340,160 )
2007	2007	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	4	4/30/2007	NON-COMPETING CONTINUATION	$340,160
														Subtotal = $340,160

Issue Date FY: 2006 ( Subtotal = $350,319 ) (Continued on the next page)
Grand Total All Awards = $9,107,220

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Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys

Award Number: R01DA017763

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2001

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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