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ROLE OF OREXIN IN COCAINE DEMAND AND ADDICTION

Award Number: R01DA006214
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/1992
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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ROLE OF OREXIN IN COCAINE DEMAND AND ADDICTION - Project Summary/Abstract A large number of studies over the last 14 years show that orexin neurons play an important role in reward processing and drug abuse. Although these studies show that orexin-1 receptor (OxR1) signaling is particularly involved in the motivation for many drugs of abuse, none have linked this system to the persistent, chronically relapsing nature of addiction. Here, we extend studies from the previous terms of this project to tackle this important issue. We recently found that the intermittent access (IntA) cocaine self-administration paradigm produces a strong, multiphenotype addiction-like state as well as increased numbers of orexin-expressing neurons. Importantly we find that the IntA-induced increase in addiction behaviors and orexin expression are persistent (>30d of abstinence). We also find that chronic administration of an OxR1 antagonist during IntA blocks the increased demand that this paradigm normally produces. Here, we propose to more fully characterize the IntA-linked addiction profile and induced-orexin neurons following 30d abstinence. We also will examine the contribution of OxR1 and OxR2 signaling in ventral tegmental area (VTA) and paraventricular thalamus (PVT), two reward-related areas previously linked to orexin function, in persistent addiction behaviors after IntA. Finally, we will test whether the FDA-approved dual orexin receptor antagonist, Belsomra™ (suvorexant), is effective in acutely decreasing addiction behaviors, and in preventing the transition from a moderate to a severe addiction profile. Together, the proposed experiments are a natural and important extension of the prior studies in this project and will represent an important step forward in the development of an orexin-based treatment for cocaine addiction.


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 = $0 )
2025	2022	RUTGERS, THE STATE UNIVERSITY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	32	1/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $533,775 )
2024	2024	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	000	34	12/11/2023	NON-COMPETING CONTINUATION	$480,398
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	001	34	4/25/2024	NON-COMPETING CONTINUATION	$53,377
														Subtotal = $533,775

Issue Date FY: 2023 ( Subtotal = $533,775 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	002	33	1/27/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$53,377
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	001	33	12/2/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$480,398
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	32	12/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $533,775

Issue Date FY: 2022 ( Subtotal = $527,495 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	32	11/24/2021	NON-COMPETING CONTINUATION	$501,120
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	32	3/18/2022	NON-COMPETING CONTINUATION	$26,375
														Subtotal = $527,495

Issue Date FY: 2021 ( Subtotal = $520,634 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	31	3/2/2021	NON-COMPETING CONTINUATION	$52,064
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	31	11/6/2020	NON-COMPETING CONTINUATION	$468,570
														Subtotal = $520,634

Issue Date FY: 2020 ( Subtotal = $519,248 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	30	2/19/2020	COMPETING CONTINUATION	$519,248
2020	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	29	2/10/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $519,248

Issue Date FY: 2018 ( Subtotal = $434,773 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	29	5/24/2018	NON-COMPETING CONTINUATION	$43,479
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	29	2/28/2018	NON-COMPETING CONTINUATION	$391,294
														Subtotal = $434,773

Issue Date FY: 2017 ( Subtotal = $437,476 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	28	2/15/2017	NON-COMPETING CONTINUATION	$393,727
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	28	5/22/2017	NON-COMPETING CONTINUATION	$43,749
														Subtotal = $437,476

Issue Date FY: 2016 ( Subtotal = $446,255 )
2016	2016	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	27	2/25/2016	NON-COMPETING CONTINUATION	$446,255
														Subtotal = $446,255

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2015	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	26	5/14/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$571,934
2015	2015	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	26	5/18/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$571,934
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $568,187 )
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	25	3/4/2014	COMPETING CONTINUATION	-$431,145
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	002	25	3/12/2014	COMPETING CONTINUATION	$431,145
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	004	25	3/19/2014	SUPPLEMENT FOR EXPANSION	$137,042
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 Ashley Ave	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	003	25	3/14/2014	COMPETING CONTINUATION	$0
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	25	2/26/2014	COMPETING CONTINUATION	$431,145
														Subtotal = $568,187

Issue Date FY: 2002 ( Subtotal = $342,755 )
2002	2002	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	13	4/5/2002	NON-COMPETING CONTINUATION	$342,755
														Subtotal = $342,755

Issue Date FY: 2001 ( Subtotal = $334,826 )
2001	2001	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	12	4/20/2001	NON-COMPETING CONTINUATION	$269,778
2001	2001	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	001	12	9/6/2001	SUPPLEMENT FOR EXPANSION	$65,048
														Subtotal = $334,826

Issue Date FY: 2000 ( Subtotal = $262,949 )
2000	2000	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	11	3/13/2000	NON-COMPETING CONTINUATION	$262,949
														Subtotal = $262,949

Issue Date FY: 1999 ( Subtotal = $254,489 )
1999	1999	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	10	4/6/1999	NON-COMPETING CONTINUATION	$254,489
														Subtotal = $254,489

Issue Date FY: 1998 ( Subtotal = $247,662 )
1998	1998	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	9	5/5/1998	COMPETING CONTINUATION	$247,662
														Subtotal = $247,662

Grand Total All Awards = $5,964,299

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ROLE OF OREXIN IN COCAINE DEMAND AND ADDICTION

Award Number: R01DA006214

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/1992

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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