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Examining nicotine relapse in the habenulo-interpeduncular system

Award Number: R01DA040626
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Examining nicotine relapse in the habenulo-interpeduncular system - PROJECT SUMMARY Chronic exposure to nicotine in tobacco products results in numerous health consequences (lung cancer, emphysema, hypertension, etc.) and accounts for over 6 million deaths per year. Relapse rates are high among those who attempt to quit smoking, and pharmacotherapies that seek to foster smoking cessation have limited effectiveness. Thus, there is a significant unmet need for more effective strategies to treat nicotine dependence. Nicotine exposure produces physical dependence, and the physical and/or emotional nicotine withdrawal symptoms – as compared to the rewarding effects of nicotine – are often the most important contributors to relapse. Importantly, nicotine cravings and the risk for relapse tend to peak 1 to 2 weeks after the beginning of abstinence. Unfortunately, few research studies have probed the important question of how/why relapse behavior develops. Indeed, a critical gap in knowledge exists regarding our understanding of how chronic nicotine exposure encourages nicotine seeking during abstinence. In this project, we will use a rat nicotine self- administration model to study the medial habenula (MHb) and interpeduncular nucleus (IPN), which together comprise a crucial pathway involved in nicotine-related behaviors. Nicotinic acetylcholine receptors (nAChRs), the pharmacological target of nicotine, are densely expressed in this pathway and are responsible for nicotine's psychoactive and addictive properties. In this project, we intend to identify the relevant nAChRs and brain circuits involved in nicotine seeking during abstinence. Three independent and complementary AIMs are proposed, each of which probes a specific mechanistic aspect of relapse-like behavior. In AIM 1, we will use biophysical techniques, 2-photon imaging, and fiber photometry to probe the relationship between MHb neuronal activity and nicotine seeking during abstinence. AIM 2 will use electrophysiology, 2-photon imaging, and a DREADD approach to examine the role of IPN neurons in nicotine seeking. Finally, AIM 3 will identify specific IPN nAChRs involved in nicotine seeking and determine the importance of nicotinic cholinergic receptor activity in producing nicotine craving and resultant nicotine seeking. Together, these AIMs will help us understand how cessation of nicotine intake causes the brain to generate aversive physical and emotional withdrawal responses that inevitably lead to relapse. Solving this problem could lead to new strategies or drugs to foster smoking cessation.


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 = $454,086 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	9	4/14/2025	NON-COMPETING CONTINUATION	$45,408
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	9	3/24/2025	NON-COMPETING CONTINUATION	$408,678
														Subtotal = $454,086

Issue Date FY: 2024 ( Subtotal = $454,086 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	8	4/25/2024	NON-COMPETING CONTINUATION	$45,408
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	8	3/13/2024	NON-COMPETING CONTINUATION	$408,678
														Subtotal = $454,086

Issue Date FY: 2023 ( Subtotal = $454,086 )
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	7	3/23/2023	NON-COMPETING CONTINUATION	$454,086
2023	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	002	6	6/29/2023	COMPETING CONTINUATION	$173,143
2023	2020	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	5	6/29/2023	NON-COMPETING CONTINUATION	-$173,143
														Subtotal = $454,086

Issue Date FY: 2022 ( Subtotal = $454,086 )
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	6	3/8/2022	COMPETING CONTINUATION	$454,086
														Subtotal = $454,086

Issue Date FY: 2020 ( Subtotal = $348,750 )
2020	2020	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	5	5/28/2020	NON-COMPETING CONTINUATION	$348,750
														Subtotal = $348,750

Issue Date FY: 2019 ( Subtotal = $348,750 )
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	004	4	9/26/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$170,328
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	002	4	8/27/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$348,750
2019	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Drug Use and Addiction Research Programs	001	3	8/27/2019	NON-COMPETING CONTINUATION	$0
2019	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Drug Use and Addiction Research Programs	003	3	9/26/2019	NON-COMPETING CONTINUATION	-$170,328
2019	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Drug Use and Addiction Research Programs	000	3	8/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $348,750

Issue Date FY: 2018 ( Subtotal = $350,005 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Drug Use and Addiction Research Programs	000	3	5/17/2018	NON-COMPETING CONTINUATION	$350,005
														Subtotal = $350,005

Issue Date FY: 2017 ( Subtotal = $349,806 )
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Drug Use and Addiction Research Programs	000	2	5/24/2017	NON-COMPETING CONTINUATION	$349,806
														Subtotal = $349,806

Issue Date FY: 2016 ( Subtotal = $346,728 )
2016	2016	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Drug Use and Addiction Research Programs	000	1	7/27/2016	NEW	$346,728
														Subtotal = $346,728

Grand Total All Awards = $3,560,383

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Examining nicotine relapse in the habenulo-interpeduncular system

Award Number: R01DA040626

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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