# Anatomical Basis for Nicotine Addiction

> **NIH NIH R37** · YALE UNIVERSITY · 2021 · $376,875

## Abstract

Abstract
Despite the necessary role of dopamine in nicotine reinforcement, it is not sufficient to explain the complexity of
addiction. Additional processes, particularly the ability of cues associated with nicotine exposure to develop
control over behavior, are essential for ongoing drug seeking. Both human subjects and rodents experience
reward-enhancement when exposed to nicotine. This has led to the idea that one of the primary factors driving
nicotine addiction is its ability to potentiate the value of other appetitive stimuli and to accelerate cue-reward
learning. In this proposal, we will investigate novel, circuit-level mechanisms that may underlie the ability of
nicotine to potentiate responding for appetitive stimuli. We have discovered two, potentially interacting,
microcircuits that increase responding for rewards and reward-paired cues, and have used proteomic,
transcriptomic epigenomic approaches to identify intracellular pathways downstream of nAChRs that contribute
to cellular and morphological plasticity following nicotine administration and could underlie potentiated cue-
reward responding. Our Aims are to determine the role of a ventral tegmental area to ventral pallidum, and a
basal forebrain to basolateral amygdala pathway, in enhanced cue-reward behavior, to determine whether
these pathways interact, and to identify effects of nicotine on these circuits, as well as signaling pathways
involved in neuronal plasticity that could maintain long-term changes in reward-related behaviors. Together,
these proposed studies will go beyond initial steps of nicotine reward mediated through DA signaling to identify
circuits and signaling pathways involved in the ability of nicotine to potentiate rewarding responses, processes
that likely contribute to long-term susceptibility to nicotine addiction and relapse.

## Key facts

- **NIH application ID:** 10134300
- **Project number:** 5R37DA014241-17
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Marina R Picciotto
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,875
- **Award type:** 5
- **Project period:** 2001-09-30 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134300

## Citation

> US National Institutes of Health, RePORTER application 10134300, Anatomical Basis for Nicotine Addiction (5R37DA014241-17). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10134300. Licensed CC0.

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