Tuesday, April 23, 2024 4/23/2024

Inhibitory synaptic transmission, stress, and drugs of abuse

Award Number: R01DA011289
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Relapse is a central problem associated with the treatment of drug addiction. Exposure to brief stress can enhance craving and trigger relapse in humans, and triggers robust relapse to drug-seeking behavior in animal models. Recent work over the past ten years from our lab and others' has shown that a single exposure to an addictive drug can either initiate or block forms of synaptic plasticity in the ventral tegmental area (VTA), a region known to be critical in relapse to drug-seeking. We found that brief acute stress blocks synaptic plasticity at GABAergic synapses on VTA dopamine neurons (LTPGABA), and have characterized the molecular cascades involved. A single stressful experience activates kappa opioid receptors (¿ORs), and we showed that interrupting kappa receptor signaling rescues the LTP in brain slice recordings - but also importantly, prevents stress-induced reinstatement of drug-seeking. We have recently found that interrupting ¿OR signaling even days after the stressor both rescues LTP in dopamine neurons in vitro and prevents reinstatement of drug seeking in behavioral tests. While all the mechanistic steps are not yet known, all of our data support the general idea that removal of this normal brake on VTA dopamine neurons contributes to reinstatement. In this application, we will identify the circuits involved, asking: 1) which GABAergic afferents normally exhibit LTPGABA and lose it after acute stress, and 2) which dynorphin-releasing afferents and ¿ORs are active during acute stress and alter the VTA circuit to drive relapse behavior. Knowing the brain regions and specific pathways involved offers the opportunity to manipulate these towards therapy development.


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: 2023 ( Subtotal = $442,084 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Drug Abuse and Addiction Research Programs	000	23	4/20/2023	NON-COMPETING CONTINUATION	$442,084
														Subtotal = $442,084

Issue Date FY: 2022 ( Subtotal = $442,084 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Drug Abuse and Addiction Research Programs	000	22	4/21/2022	NON-COMPETING CONTINUATION	$442,084
														Subtotal = $442,084

Issue Date FY: 2021 ( Subtotal = $462,831 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Drug Abuse and Addiction Research Programs	000	21	5/4/2021	NON-COMPETING CONTINUATION	$462,831
														Subtotal = $462,831

Issue Date FY: 2020 ( Subtotal = $349,697 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Drug Abuse and Addiction Research Programs	000	20	4/17/2020	NON-COMPETING CONTINUATION	$349,697
														Subtotal = $349,697

Issue Date FY: 2019 ( Subtotal = $349,697 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Drug Abuse and Addiction Research Programs	000	19	5/28/2019	COMPETING CONTINUATION	$349,697
														Subtotal = $349,697

Issue Date FY: 2018 ( Subtotal = -$30,685 )
2018	2016	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	18	3/14/2018	EXTENSION WITH OR WITHOUT FUNDS	-$30,685
														Subtotal = -$30,685

Issue Date FY: 2016 ( Subtotal = $329,286 )
2016	2016	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	18	2/9/2016	EXTENSION WITH OR WITHOUT FUNDS	$329,286
														Subtotal = $329,286

Issue Date FY: 2015 ( Subtotal = $337,719 )
2015	2015	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	001	17	2/16/2015	NON-COMPETING CONTINUATION	$29,143
2015	2015	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	17	1/23/2015	NON-COMPETING CONTINUATION	$308,576
														Subtotal = $337,719

Issue Date FY: 2014 ( Subtotal = $330,563 )
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	001	16	2/20/2014	NON-COMPETING CONTINUATION	$33,057
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	16	12/18/2013	NON-COMPETING CONTINUATION	$297,506
														Subtotal = $330,563

Issue Date FY: 2013 ( Subtotal = $438,733 )
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	002	15	9/4/2013	SUPPLEMENT FOR EXPANSION	$121,875
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	15	11/30/2012	NON-COMPETING CONTINUATION	$297,054
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	001	15	5/16/2013	NON-COMPETING CONTINUATION	$19,804
														Subtotal = $438,733

Issue Date FY: 2012 ( Subtotal = $327,016 )
2012	2012	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	001	14	1/9/2012	COMPETING CONTINUATION	$327,016
2012	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	13	1/6/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $327,016

Issue Date FY: 2010 ( Subtotal = $288,393 )
2010	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	13	3/8/2010	NON-COMPETING CONTINUATION	$288,393
														Subtotal = $288,393

Issue Date FY: 2009 ( Subtotal = $370,051 )
2009	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	12	4/2/2009	NON-COMPETING CONTINUATION	$370,051
														Subtotal = $370,051

Issue Date FY: 2008 ( Subtotal = $367,888 )
2008	2008	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	11	3/13/2008	NON-COMPETING CONTINUATION	$291,568
2008	2008	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	001	11	4/30/2008	SUPPLEMENT FOR EXPANSION	$76,320
														Subtotal = $367,888

Issue Date FY: 2007 ( Subtotal = $296,986 )
2007	2007	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	10	3/30/2007	NON-COMPETING CONTINUATION	$296,986
														Subtotal = $296,986

Issue Date FY: 2006 ( Subtotal = $302,822 )
2006	2006	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	9	3/25/2006	COMPETING CONTINUATION	$302,822
														Subtotal = $302,822

Issue Date FY: 2004 ( Subtotal = $274,750 )
2004	2004	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	8	4/5/2004	NON-COMPETING CONTINUATION	$274,750
														Subtotal = $274,750

Issue Date FY: 2003 ( Subtotal = $274,750 )
2003	2003	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	7		NON-COMPETING CONTINUATION	$274,750
														Subtotal = $274,750

Issue Date FY: 2002 ( Subtotal = $274,750 )
2002	2002	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	6	4/3/2002	NON-COMPETING CONTINUATION	$274,750
														Subtotal = $274,750

Issue Date FY: 2001 ( Subtotal = $275,188 )
2001	2001	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	5	3/13/2001	NON-COMPETING CONTINUATION	$275,188
														Subtotal = $275,188

Issue Date FY: 2000 ( Subtotal = $288,854 )
2000	2000	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Drug Abuse and Addiction Research Programs	000	4	6/20/2000	COMPETING CONTINUATION	$288,854
														Subtotal = $288,854

Issue Date FY: 1999 ( Subtotal = $128,599 )
1999	1999	Duke University	OFFICE OF SPONSORED PROGRAMS	DURHAM	NC	27705	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	3	5/12/1999	NON-COMPETING CONTINUATION	$128,599
														Subtotal = $128,599

Grand Total All Awards = $7,046,910

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Inhibitory synaptic transmission, stress, and drugs of abuse

Award Number: R01DA011289

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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