# Oleoyl Glycine-induced reduction of Nicotine Seeking: Bioanalytical & Behavioral Approaches

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $40,689

## Abstract

PROJECT SUMMARY
Tobacco use continues to be a substantial public health issue with more than 16 million individuals in the United
States suffering from a tobacco-related disease. While there are currently seven nicotine cessation
pharmacotherapies approved by the Food and Drug Administration, nicotine cessation success rates remain
low. Varenicline is considered to be the most effective treatment with a cessation success rate estimated at 26%.
A majority of smokers report a desire to quit smoking, and yet even with current treatments most are unsuccessful
in their attempts. With the deleterious health effects of tobacco and the current disparity between smokers’ desire
and ability to quit smoking, research into novel nicotine addiction treatments is critical for improvement of public
health. A recent study highlighted a novel endogenous compound demonstrating promise as a nicotine cessation
treatment in murine models of nicotine reward and withdrawal. Following a report in which tobacco smokers
who sustained ischemic injury to their insular cortex reported reduced craving and less severe withdrawal
symptoms compared to smokers with injury to other brain areas, a mouse model of mild traumatic brain injury
was employed to identify neurochemicals that may offset nicotine reward and dependence. In the model, n-
oleoyl glycine (OlGly) was discovered to be increased in the insular cortex. In addition to the report in smokers
with ischemic stroke, other human imaging and animal studies suggest the insular cortex plays a role in drug
addiction, craving, and seeking. Subsequently, exogenous administration of the n-acyl amino acid, OlGly,
prevented nicotine-induced conditioned place preference (CPP) through a peroxisome proliferator-activated
receptor alpha (PPAR-α) dependent mechanism and ameliorated mecamylamine-precipitated nicotine
withdrawal in mouse models. Here, we hypothesize: exogenous OlGly reduces nicotine seeking behavior
through direct actions in the insular cortex to dampen nicotine-induced dopamine release. Aim 1 will determine
if the insular cortex is critical for the attenuation of nicotine seeking behavior by OlGly and if repeated nicotine
exposure dysregulates OlGly in the insular cortex. Aim 2 will utilize in vivo G-protein coupled receptor dopamine
sensors to investigate whether OlGly reduces nicotine-induced dopamine release in the nucleus accumbens.
Completion of the proposed research will lead to an increased understanding of neural substrates and underlying
mechanisms of action involved in the attenuation of nicotine seeking by OlGly, as well as the role of OlGly in
nicotine addiction.

## Key facts

- **NIH application ID:** 10537810
- **Project number:** 1F31DA056228-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Kimberly Nicole Karin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,689
- **Award type:** 1
- **Project period:** 2022-08-25 → 2024-08-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537810

## Citation

> US National Institutes of Health, RePORTER application 10537810, Oleoyl Glycine-induced reduction of Nicotine Seeking: Bioanalytical & Behavioral Approaches (1F31DA056228-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10537810. Licensed CC0.

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