# Genetic basis of nicotine withdrawal in a reduced complexity cross

> **NIH NIH U01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $585,690

## Abstract

Project Summary
Despite evidence of strong genetic contributions to the etiology of nicotine dependence
(ND), we are far from identifying the specific genetic bases of individual susceptibility to
ND. The primary objective of this proposal is to identify novel genetic factors that
contribute to nicotine withdrawal, an important aspect of ND that contribute relapse, in
mice. We observed pronounced nicotine withdrawal traits differences in C57BL/6NJ
strain but not in the closely related C57BL/6J substrain. Because the parental substrains
are nearly genetically identical, quantitative trait locus (QTL) mapping in an experimental
F2 cross (Reduced Complexity Cross; RCC) will greatly facilitate the identification of
novel genetic factors that underlie differences in withdrawal behaviors. In Aim 1, we will
use the RCC to map genomic regions, or QTLs, that are causally associated with
susceptibility versus resilience to multiple measures of nicotine withdrawal. In Aim 2, we
will conduct transcriptome analysis via mRNA sequencing (RNA-seq) of four brain
regions regions in control mice and chronic nicotine-treated mice from the parental male
and female C57BL/6J and C57BL/6NJ substrains. The transcriptome in control mice will
serve as a useful tool both in identifying candidate genes for future genome editing that
are differentially expressed and underlie the behavioral QTLs as well as providing
genomic insight into the neuronal context that influences susceptibility versus resilience
to nicotine withdrawal. Genes that are differentially expressed as a consequence of
nicotine will reveal changes in the transcriptome relevant to central neuronal plasticity
and the behaviors/changes that support ND. In Aim 3, we will validate candidate
quantitative trait genes and functional variants identified and ranked by Aims 1-2.

## Key facts

- **NIH application ID:** 9920699
- **Project number:** 5U01DA045299-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** M. Imad Damaj
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $585,690
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920699

## Citation

> US National Institutes of Health, RePORTER application 9920699, Genetic basis of nicotine withdrawal in a reduced complexity cross (5U01DA045299-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920699. Licensed CC0.

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