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Neuropeptides, Social Stress and Drugs of Abuse

Award Number: R01DA031734
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2011
PERIOD OF PERFORMANCE END DATE: 11/30/2022

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Neuropeptides, Social Stress and Drugs of Abuse - Project Summary The rationale for the current specific aims builds on the consistent epidemiological finding that social stress contributes critically to all phases of the addiction cycle, from initiation to escalation to relapse. The close link between social stress and drug use is based on reports from emergency rooms treating victims of violence and statistics from the criminal justice system on violent crimes committed by drug users as well as epidemiological evidence and neurobiological data. The overarching question to be answered by the proposed research is: what is the mechanistic link between social stress and escalated cocaine self-administration? Our special emphasis is on how corticotropin releasing factor (CRF, often referred to as CRH) modulates mesocorticolimbic dopamine (DA) systems. The CRF system is of continued interest, not only because it is critical to the initiation of the endocrine stress response, but its extra-hypothalamic localization and action are of significance in stress disorders and represent potential targets for therapeutic intervention. Specific Aim One tests the hypothesis that highly aversive social stress amplifies intensely rewarding cocaine self-administration by action on CRF and dopamine (DA) in microcircuits from the posterior ventral tegmental area (pVTA) to the dorsal raphe nuclei (DRN). Neuroanatomical tract tracing is employed to identify the synaptic contacts with DA neurons as a source of CRF input. In vivo microdialysis in the terminals of these microcircuits are used to characterize the dynamic neuroadaptions that contribute to the stress-induced escalation of cocaine self-administration (acquisition, maintenance, binge, relapse). Specific Aim Two tests the hypothesis that activation and inhibition of specific CRF cell groups in the VTA- DRN microcircuit modulate cocaine self-administration. In vivo optogenetics and, in parallel, Gq- or Gi- DREADD in mice expressing Channelrhodopsin specifically in CRF neurons (ChR/Crh mice) will be used to activate CRF inputs into the VTA or inhibit with archaerhodopsin. Microinjections CRFR1, CRFR2 and binding protein antagonists and agonists into the VTA-DRN microcircuit will identify targets for preventing and reversing effects of social defeat stress or optogenetic activation that escalate cocaine self-administration. A special feature of the proposed work is the test of the hypothesis that social stress-escalated cocaine self-administration is buffered in a sex-specific manner.


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 = -$611 )
2025	2021	TRUSTEES OF TUFTS COLLEGE	80 GEORGE ST	MEDFORD	MA	02155	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	10	4/23/2025	NON-COMPETING CONTINUATION	-$587
2025	2021	TRUSTEES OF TUFTS COLLEGE	80 GEORGE ST	MEDFORD	MA	02155	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	10	4/23/2025	SUPPLEMENT FOR EXPANSION	-$24
														Subtotal = -$611

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	TRUSTEES OF TUFTS COLLEGE	169 HOLLAND ST	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	10	4/9/2024	NON-COMPETING CONTINUATION	$0
2024	2021	TRUSTEES OF TUFTS COLLEGE	169 HOLLAND ST	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	10	7/8/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	10	12/12/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $350,380 )
2021	2021	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	10	2/19/2021	NON-COMPETING CONTINUATION	$33,666
2021	2021	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	002	10	5/27/2021	SUPPLEMENT FOR EXPANSION	$13,728
2021	2021	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	10	11/19/2020	NON-COMPETING CONTINUATION	$302,986
														Subtotal = $350,380

Issue Date FY: 2020 ( Subtotal = $336,652 )
2020	2020	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	9	11/21/2019	NON-COMPETING CONTINUATION	$302,986
2020	2020	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	9	2/11/2020	NON-COMPETING CONTINUATION	$33,666
														Subtotal = $336,652

Issue Date FY: 2019 ( Subtotal = $336,652 )
2019	2019	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	8	11/5/2018	NON-COMPETING CONTINUATION	$336,652
														Subtotal = $336,652

Issue Date FY: 2018 ( Subtotal = $336,652 )
2018	2018	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	7	11/15/2017	NON-COMPETING CONTINUATION	$302,986
2018	2018	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	7	4/26/2018	NON-COMPETING CONTINUATION	$33,666
														Subtotal = $336,652

Issue Date FY: 2017 ( Subtotal = $336,652 )
2017	2017	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	002	6	3/27/2017	COMPETING CONTINUATION	$12,454
2017	2017	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	6	1/16/2017	COMPETING CONTINUATION	$336,652
2017	2015	TRUSTEES OF TUFTS COLLEGE INC	169 HOLLAND ST FL 3	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	5	3/27/2017	NON-COMPETING CONTINUATION	-$12,454
														Subtotal = $336,652

Issue Date FY: 2015 ( Subtotal = $299,554 )
2015	2015	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	5	5/1/2015	NON-COMPETING CONTINUATION	$299,554
														Subtotal = $299,554

Issue Date FY: 2014 ( Subtotal = $304,227 )
2014	2014	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	4	7/14/2014	NON-COMPETING CONTINUATION	$304,227
														Subtotal = $304,227

Issue Date FY: 2013 ( Subtotal = $333,420 )
2013	2013	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	3	5/28/2013	NON-COMPETING CONTINUATION	$333,420
														Subtotal = $333,420

Issue Date FY: 2012 ( Subtotal = $347,416 )
2012	2012	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	001	2	5/18/2012	SUPPLEMENT FOR EXPANSION	$42,980
2012	2012	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	2	5/15/2012	NON-COMPETING CONTINUATION	$304,436
														Subtotal = $347,416

Issue Date FY: 2011 ( Subtotal = $304,534 )
2011	2011	TUFTS UNIVERSITY	169 HOLLAND ST, 2ND FLOOR	SOMERVILLE	MA	02144	MIDDLESEX	USA	Drug Use and Addiction Research Programs	000	1	6/25/2011	NEW	$304,534
														Subtotal = $304,534

Grand Total All Awards = $3,285,528

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Neuropeptides, Social Stress and Drugs of Abuse

Award Number: R01DA031734

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2011

PERIOD OF PERFORMANCE END DATE: 11/30/2022

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