# Adolescent Exposure to Stress or Nicotine Increases Rodent Alcohol Self-Administration

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $485,541

## Abstract

Project Summary.
 Excessive alcohol use is among the leading causes of preventable death worldwide and costs the USA
over $223 billion a year. Stress and nicotine (from tobacco) are well-known risk factors for heavy alcohol
consumption and alcohol use disorders. Despite the consistent human epidemiological evidence, in
experimental models stress does not always produce increased alcohol consumption. The controversy arises,
in part, because the neural mechanisms underlying the interactions among stress, nicotine, and alcohol remain
significantly unknown.
 This proposal arose from our preliminary results showing that pre-exposure to acute nicotine or stress
under strictly defined experimental conditions increases alcohol self-administration. We showed in rats that
nicotine (like stress) boosts corticosterone levels in rats. Nicotine- or stress-induced glucocorticoid receptor
activity is necessary for the subsequent increase in alcohol self-administration that arises owing to altered
midbrain GABAergic circuitry. When we inhibited the nicotine/stress-induced glucocorticoid signaling or
corrected midbrain GABAergic dysfunction, then alcohol self-administration returned to control levels.
 In the proposed studies, we will move from the simple acute exposures to nicotine and stress to more
biologically realistic experimental situations. Lifetime nicotine and tobacco use almost always begins during
adolescence, and adolescent smoking and childhood maltreatment are both high risk factors for increased
alcohol consumption and alcohol use disorders in adulthood. Therefore, we will expose adolescent rats to
nicotine or stress then allow the animals to age before analyzing their alcohol drinking behavior compared to
control rats. Our preliminary results with adolescent nicotine treatments show that later in life, the adolescent-
treated rats do drink more alcohol. Furthermore, the increased drinking requires glucocorticoid activity and
arises from changes in midbrain GABAergic circuitry. We will measure the consequences of adolescent stress
or nicotine exposure in adult rats during initiation, maintenance, extinction, and re-instatement of alcohol self-
administration.
 The experiments will go on to investigate general circuit mechanisms underlying the increase in alcohol
self-administration induced by adolescent nicotine or stress. Initially, we will be guided by our recent results
indicating that a single, acute exposure to nicotine or stress induces an increase in alcohol self-administration
by altering midbrain GABAergic circuitry. Then, guided by our preliminary results we will prevent or reverse the
increased drinking caused by adolescent stress or nicotine via molecular and pharmacological manipulations
within the midbrain. An aim is to identify a target and test a potential therapeutic drug to aid against increased
alcohol consumption.

## Key facts

- **NIH application ID:** 9993178
- **Project number:** 5R01AA026267-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** John A. Dani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,541
- **Award type:** 5
- **Project period:** 2019-08-10 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993178

## Citation

> US National Institutes of Health, RePORTER application 9993178, Adolescent Exposure to Stress or Nicotine Increases Rodent Alcohol Self-Administration (5R01AA026267-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993178. Licensed CC0.

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