# Project 3: Adolescent Nicotine

> **NIH NIH P50** · JACKSON LABORATORY · 2020 · $150,431

## Abstract

PROJECT SUMMARY PROJECT 3 – ADOLESCENT NICOTINE
Nicotine is one of the most commonly used drugs among adolescents. Several studies link tobacco and
nicotine use in human adolescence and subsequent problems in adulthood, including later tobacco, alcohol,
cocaine and other illicit drug use. Individuals who smoke cigarettes before the age of 15 are estimated to be
eighty times more likely to use illegal drugs such as cocaine than those who do not. In addition, studies in
animals have shown that adolescent nicotine exposure affects nicotine and cocaine reward and sensitivity in
rodents; we have shown that repeated exposure to low doses of nicotine in adolescence clearly induces age-
specific enhancement of the rewarding effects of nicotine and other drugs of abuse that persisted long after the
termination of nicotine exposure. However, the molecular and genetic mechanisms underlining nicotine-
induced enhancements to the reward effects are still unclear. This project will identify risk associated genes
and gene networks using highly diverse mouse genetic populations. We will use inbred Collaborative Cross
(CC)/ Diversity Outcross (DO) founder and CC strains to measure nicotine reward using the conditioned place
preference (CPP) test after exposure to nicotine in early adolescence. These data will be used to conduct
genetic correlations across behaviors including impulsivity, cocaine self-administration (IVSA), acute and
sensitized cocaine induced locomotor activation and circadian rhythms to determine common genetic
architecture shared among traits. We will also study changes in striatal dopamine (DA) signaling in CC strains
that exhibit extreme behavioral responses to nicotine. Secondly, we will correlate nicotine CPP behaviors with
gene expression changes in the striatum of CC mice to further identify potential candidate genes, gene
networks and biological mechanisms that may mediate the effects of adolescent nicotine exposure. Finally, we
will map nicotine reward in the CPP test in a large DO cohort after exposure to nicotine during early
adolescence. Genotype data will be used to reveal QTLs specific to nicotine in adolescence as well as identify
common QTLs shared between impulsivity, cocaine self-administration, cocaine sensitization and circadian
rhythms phenotypes generated by the various projects and cores within the Center for Systems Neurogenetics
of Addiction. Genetic mapping data along with expression studies will be used to identify candidate genes for
validation studies in novel mouse models made through genome editing technologies. If successful, this
application promises to have a significant positive impact on human health through the identification of
genetically high-risk individuals who would benefit from proactive interventions following nicotine exposure in
adolescence.

## Key facts

- **NIH application ID:** 9933851
- **Project number:** 5P50DA039841-05
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** M. Imad Damaj
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,431
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933851

## Citation

> US National Institutes of Health, RePORTER application 9933851, Project 3: Adolescent Nicotine (5P50DA039841-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933851. Licensed CC0.

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