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Glutamate and Craving for Cocaine

Award Number: R01DA012513
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/10/2000
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Glutamate and Craving for Cocaine - Project Summary A treatment for drug addiction remains elusive due to incomplete knowledge of the brain circuits controlling both the overwhelming motivation to relapse to drug use and the ability to refrain from using drugs. In part through progress during the 20-yr tenure of this grant, we know that glutamatergic projections from cortical and allocortical brain regions to the nucleus accumbens core (NAcore) and GABAergic NAcore projections to the dorsolateral ventral pallidum (dlVP) are necessary for executing cue-induced cocaine seeking and extinction training-induced refraining from cocaine seeking. Classically, projections from the striatum contain two neuronal subtypes, those projecting to the ventral mesencephalon selectively expressing D1 dopamine receptors (D1-MSNs) and those projecting to the palldum expressing D2 receptors (D2-MSNs). Through work on this grant, we now know that NAcore D1-MSNs also innervate the dlVP1, and that activity in this D1-MSN to dlVP subcircuit is necessary for cue- induced cocaine seeking. Also, we discovered that activity in D2-MSNs is associated with extinction-induced refraining from cocaine seeking. Akin to the NAcore, the dlVP contains two primary cell types, one expressing glutamate (VPglu) and the other expressing GABA (VPGABA). Also, a subpopulation of VPGABA co-express enkephalin (VPPenk). We have begun to study the dlVP subcircuits coded by these distinct dlVP neuronal subtypes in regulating cocaine seeking and refraining from seeking. Cell-type specific chemogenetic stimulation reveals that VPglu inhibit reinstated cocaine seeking and stimulating VPPenk induces cocaine seeking. Surprisingly, VPglu and VPGABA cells in dlVP have different axon terminal fields. These findings indicate distinct roles for the different dlVP neuronal subtypes, and that divergent roles for subtype selective projections emanating from the dlVP is likely. We propose to disentangle the circuitry in which the dlVP is embedded using a combination of behavior, in vivo calcium imaging and slice electrophysiology, and test the hypothesis that VPglu activity promotes refraining during extinction responding, while VPPenk codes for cocaine seeking.


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: 2024 ( Subtotal = $368,230 )
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	25	3/19/2024	NON-COMPETING CONTINUATION	$331,407
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	25	4/25/2024	NON-COMPETING CONTINUATION	$36,823
														Subtotal = $368,230

Issue Date FY: 2023 ( Subtotal = $368,230 )
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	24	3/23/2023	NON-COMPETING CONTINUATION	$368,230
														Subtotal = $368,230

Issue Date FY: 2022 ( Subtotal = $368,230 )
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	23	4/1/2022	NON-COMPETING CONTINUATION	$368,230
														Subtotal = $368,230

Issue Date FY: 2021 ( Subtotal = $368,230 )
2021	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	002	22	3/29/2021	NON-COMPETING CONTINUATION	$368,230
2021	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	21	2/2/2021	COMPETING CONTINUATION	$96,543
2021	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	20	2/2/2021	NON-COMPETING CONTINUATION	-$96,543
														Subtotal = $368,230

Issue Date FY: 2020 ( Subtotal = $376,746 )
2020	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	21	6/26/2020	COMPETING CONTINUATION	$376,746
2020	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	20	6/26/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $376,746

Issue Date FY: 2019 ( Subtotal = $335,039 )
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	20	3/19/2019	NON-COMPETING CONTINUATION	$335,039
														Subtotal = $335,039

Issue Date FY: 2018 ( Subtotal = $484,538 )
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	002	19	9/12/2018	SUPPLEMENT FOR EXPANSION	$149,499
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	19	4/26/2018	NON-COMPETING CONTINUATION	$33,505
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	19	3/19/2018	NON-COMPETING CONTINUATION	$301,534
														Subtotal = $484,538

Issue Date FY: 2017 ( Subtotal = $335,039 )
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	18	5/22/2017	NON-COMPETING CONTINUATION	$33,505
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	18	3/22/2017	NON-COMPETING CONTINUATION	$301,534
														Subtotal = $335,039

Issue Date FY: 2016 ( Subtotal = $331,688 )
2016	2016	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	17	3/30/2016	NON-COMPETING CONTINUATION	$331,688
														Subtotal = $331,688

Issue Date FY: 2015 ( Subtotal = $409,146 )
2015	2015	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	16	5/7/2015	COMPETING CONTINUATION	$409,146
														Subtotal = $409,146

Issue Date FY: 2014 ( Subtotal = $304,034 )
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	15	3/21/2014	NON-COMPETING CONTINUATION	$304,034
														Subtotal = $304,034

Issue Date FY: 2013 ( Subtotal = $291,873 )
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	14	3/13/2013	NON-COMPETING CONTINUATION	$273,632
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	14	5/20/2013	NON-COMPETING CONTINUATION	$18,241
														Subtotal = $291,873

Issue Date FY: 2012 ( Subtotal = $304,034 )
2012	2012	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	13	3/12/2012	NON-COMPETING CONTINUATION	$304,034
														Subtotal = $304,034

Issue Date FY: 2011 ( Subtotal = $304,034 )
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	12	6/28/2011	NON-COMPETING CONTINUATION	$21,940
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	12	3/29/2011	NON-COMPETING CONTINUATION	$282,094
														Subtotal = $304,034

Issue Date FY: 2010 ( Subtotal = $313,438 )
2010	2010	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	11	3/2/2010	COMPETING CONTINUATION	$313,438
														Subtotal = $313,438

Issue Date FY: 2009 ( Subtotal = $237,414 )
2009	2009	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	10	3/27/2009	NON-COMPETING CONTINUATION	$237,414
														Subtotal = $237,414

Issue Date FY: 2008 ( Subtotal = $237,414 )
2008	2008	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	9	3/31/2008	NON-COMPETING CONTINUATION	$237,414
														Subtotal = $237,414

Issue Date FY: 2007 ( Subtotal = $242,259 )
2007	2007	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	8	4/2/2007	NON-COMPETING CONTINUATION	$242,259
														Subtotal = $242,259

Issue Date FY: 2006 ( Subtotal = $249,495 )
2006	2006	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	7	4/6/2006	NON-COMPETING CONTINUATION	$249,495
														Subtotal = $249,495

Issue Date FY: 2005 ( Subtotal = $244,000 )
2005	2005	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	6	2/16/2005	COMPETING CONTINUATION	$244,000
														Subtotal = $244,000

Issue Date FY: 2004 ( Subtotal = $207,061 ) (Continued on the next page)
Grand Total All Awards = $7,474,158

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Glutamate and Craving for Cocaine

Award Number: R01DA012513

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/10/2000

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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