# Interstrain variability in long-term cognitive effects of adolescent nicotine exposure

> **NIH NIH R03** · PENNSYLVANIA STATE UNIVERSITY, THE · 2020 · $79,930

## Abstract

PROJECT SUMMARY
Adolescent smoking is a serious public health concern. Earlier initiation of smoking is a key factor in the
development of nicotine dependence and associated mental health problems. Increasing evidence suggests
that nicotine exposure during this critical period of development may have long-term cognitive consequences.
Mouse models represent an important tool for identifying neural and genetic underpinnings of behavioral
response to nicotine exposure across development, permitting experimental control over time course and
genetic factors. The primary objective of this proposal is to identify sex and strain variability in long-term
cognitive effects of adolescent nicotine exposure. We previously identified that adolescent C57BL/6J male
mice exposed to nicotine display long-term cognitive deficits, as assessed by contextual fear conditioning,
during adulthood. However, the effect of genetics (i.e. strain) and sex on these long-term consequences of
adolescent nicotine exposure have not yet been investigated. Here, we aim to determine the interstrain
variability in long-term cognitive effects of adolescent nicotine exposure in the founder strains of the
Collaborative Cross (CC), a panel of recombinant inbred lines derived from eight genetically diverse inbred
strains: five classical inbred strains (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ) and three wild-derived strains (CAST/EiJ, PWK/PhJ, WSB/EiJ). The CC panel represents far greater genetic diversity than
previous recombinant inbred panels, and thus, represents an unprecedented opportunity for genetic analyses.
Additionally, sex differences exist in smoking behaviors and the impact of smoking on cognition; therefore both
male and female mice from each strain will be examined to identify sex effects and interactions with strain.
Studies in this proposal will use the founders of the CC to characterize phenotypic differences across inbred
strains (Aim 1) and to investigate sex differences within and across strains (Aim 2). The goal of this proposal is
to demonstrate feasibility of using the CC panel for a forward genetics mapping study of the long-term
detrimental effects of adolescent nicotine exposure. This proposal represents an important step in investigating
an understudied area of the genetic underpinnings of the long-term consequences of adolescent nicotine
exposure. Ultimately, investigating the genetic and neurobiological factors that underlie susceptibility to these
long-term consequences may aid in the development of preventative treatments.

## Key facts

- **NIH application ID:** 9978032
- **Project number:** 5R03DA048166-02
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Thomas J Gould
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,930
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978032

## Citation

> US National Institutes of Health, RePORTER application 9978032, Interstrain variability in long-term cognitive effects of adolescent nicotine exposure (5R03DA048166-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978032. Licensed CC0.

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