# Crosstalk between dopamine and glucocorticoids in high levels of nicotine intake and anhedonia in rats

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $343,125

## Abstract

SUMMARY
Smoking is addictive and most smokers would like to quit. However, even with treatment, only a small
percentage of smokers quits successfully. Clinical studies indicate that smoking cessation leads to anhedonia,
which increases the risk for relapse. Nicotine induces the release of dopamine (DA), which plays a role in
establishing habitual smoking, while the activation of stress systems has been suggested to mediate
withdrawal and anhedonia. Virtually all animal studies have been conducted with nondependent rodents that
had limited or short access to nicotine. Therefore, very little is known about the mechanisms that mediate
withdrawal and self-administration in dependent animals with high levels of nicotine intake. To develop new
smoking cessation treatments, more insight is needed into the neurobiological mechanisms that mediate
withdrawal and nicotine intake in animals that have become dependent by self-administering nicotine. The
long-term goal of this research program is to determine the adaptations in the reward system that cause high
levels of nicotine intake and anhedonia in dependent animals. The objective of our studies is to determine the
role of DA and the stress hormone corticosterone (CORT) in nicotine self-administration in dependent animals
and withdrawal-induced anhedonia. It is proposed to use an intermittent long access model to obtain high
levels of nicotine intake and induce dependence. Our preliminary studies point to a role for DA in high levels of
nicotine intake in dependent animals, and brain stress systems in the anhedonia associated with withdrawal.
Based on our studies, it is hypothesized that DA transmission and glucocorticoid receptor (GR) signaling in the
nucleus accumbens (Nacc) are pivotal for high levels of nicotine intake and anhedonia associated with nicotine
withdrawal. Three aims are proposed to test this hypothesis. 1) Determine the relationship between nicotine
intake and reward function in dependent (long access) and nondependent (short access) animals. 2)
Determine the role of DA signaling in nicotine intake in dependent and nondependent animals. 3) Determine
the role of DA-CORT interactions in the Nacc in nicotine intake and anhedonia in dependent and
nondependent animals. To investigate the relationship between nicotine intake and reward function, male and
female rats will be prepared with intravenous catheters and intracranial self-stimulation (ICSS) electrodes. The
ICSS method provides an objective measure of reward function. Dopamine antagonists and transgenic D1-Cre
and D2-Cre rats will be used to determine the role of D1 and D2 neurons in the Nacc in high levels of nicotine
intake and withdrawal. It is predicted that D1 receptors play a critical role in nicotine intake in dependent and
nondependent animals. It is also expected that blockade of GR will decrease nicotine intake in dependent
animals, prevents the decrease in DA levels in the Nacc during withdrawal, and diminishes anhedonia
ass...

## Key facts

- **NIH application ID:** 9892989
- **Project number:** 5R01DA046411-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Adriaan Willem Bruijnzeel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,125
- **Award type:** 5
- **Project period:** 2019-03-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892989

## Citation

> US National Institutes of Health, RePORTER application 9892989, Crosstalk between dopamine and glucocorticoids in high levels of nicotine intake and anhedonia in rats (5R01DA046411-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9892989. Licensed CC0.

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