Monday, June 30, 2025 6/30/2025

TAAR1 agonists for nicotine addiction

Award Number: R01DA047967
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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TAAR1 agonists for nicotine addiction - ABSTRACT Tobacco smoking remains a major public health concern globally. Although there are FDA-approved therapeutic options available, they are far from adequate to maintain long-term smoking abstinence in most smokers. Thus, discovering novel efficacious pharmacotherapies to aid in smoking cessation remains an urgent clinical need. Nicotine, the major component in tobacco that is responsible for tobacco addiction, stimulates the mesolimbic dopaminergic system via activating nicotinic acetylcholine receptors (nAChRs). Nicotine replacement therapy and the nAChR partial agonist varenicline have achieved limited clinical success by directly modulating the central nAChRs. Indirect modulation of dopaminergic system by non-dopaminergic mechanism may also be able to modulate the addiction-related effects of nicotine. Trace amine associated receptor 1 (TAAR1) has emerged as a novel target for the development of potential pharmacotherapy to treat drug addiction. In particular, our preliminary data have shown that acute TAAR1 agonist treatment is able to reduce some addiction-related effects of nicotine. The objective of the present application is to systematically assess the therapeutic potential of TAAR1 agonists on nicotine addiction. Three Specific Aims are proposed: Aim 1 will examine the effects of repeated TAAR1 agonists (full agonist RO5166017 and partial agonist RO5263397) treatment on nicotine reinforcement using a short-access (1 hour) nicotine self-administration paradigm; Aim 2 will examine the effects of TAAR1 agonists on the reinstatement and incubation of nicotine- seeking behavior in rats with a long-access (21 hours) nicotine self-administration history; Aim 3 will examine the effects of TAAR1 agonists on nicotine withdrawal in rats with a long-access (21 hours) nicotine self- administration history. Collectively, the proposed studies systematically evaluate the effects of TAAR1 agonists on four critical aspects of nicotine addiction (e.g., reinforcing effects, reinstatement, incubation and withdrawal symptoms), each of which is thought to contribute significantly to nicotine dependence and relapse. Successful execution of the proposed studies will confirm the essential role TAAR1 in mediating nicotine addiction and provide critical preclinical evidence in support of developing TAAR1 agonists are novel pharmacotherapy for 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 = -$329 )
2025	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	5	6/4/2025	NON-COMPETING CONTINUATION	-$329
														Subtotal = -$329

Issue Date FY: 2023 ( Subtotal = $395,454 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	5	1/19/2023	NON-COMPETING CONTINUATION	$395,454
														Subtotal = $395,454

Issue Date FY: 2022 ( Subtotal = $394,905 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	001	4	3/24/2022	NON-COMPETING CONTINUATION	$39,491
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	4	2/3/2022	NON-COMPETING CONTINUATION	$355,414
														Subtotal = $394,905

Issue Date FY: 2021 ( Subtotal = $394,375 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	3	2/16/2021	NON-COMPETING CONTINUATION	$394,375
														Subtotal = $394,375

Issue Date FY: 2020 ( Subtotal = $393,860 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	2	1/31/2020	NON-COMPETING CONTINUATION	$393,860
														Subtotal = $393,860

Issue Date FY: 2019 ( Subtotal = $407,489 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	1	3/13/2019	NEW	$407,489
														Subtotal = $407,489

Grand Total All Awards = $1,985,754

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TAAR1 agonists for nicotine addiction

Award Number: R01DA047967

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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