# TAAR1 agonists for nicotine addiction

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $393,860

## Abstract

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.

## Key facts

- **NIH application ID:** 9892992
- **Project number:** 5R01DA047967-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Jun-Xu Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,860
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892992

## Citation

> US National Institutes of Health, RePORTER application 9892992, TAAR1 agonists for nicotine addiction (5R01DA047967-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892992. Licensed CC0.

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