# Brain Circuit Mechanisms for Reward Cue Attraction

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2020 · $502,243

## Abstract

Drug addiction involves an excessive motivation to pursue and consume drugs. Part of
this motivation is thought to involve the attribution of value to drug-paired cues. Cues for
rewards, including drugs and food, can become motivational targets and attract attention and
behavior. In the brain, a basic sketch of areas responsible for this process is known and
includes the nucleus accumbens (NAc) and ventral pallidum (VP). Although these areas are
bidirectionally connected as a circuit, little is known about how motivation arises out of their
circuit dynamics. To address this, the proposed research will incorporate a method called
chemogenetics for relatively non-invasive “remote control” perturbation of brain activity.
Combining this method with transgenic delivery strategies, we will both increase and decrease
activity in pathways connecting the NAc and VP to evaluate their role in the motivational
attraction to reward cues.
 This motivational process is exemplified by sign-tracking behavior, in which animals
appetitively engage with a cue predicting reward. In the proposed research, connections
between the NAc and VP will be manipulated using DREADDs to assess the role of these
pathways in acquiring and expressing the sign-tracking behavior. Recordings of neural activity
and gene expression assays will complement these experiments in order to establish neural
activation patterns that change in register with changes in motivated behavior. We will similarly
test the role of neurons in the VP expressing acetylcholine, which receive NAc input and are
hypothesized to guide attention towards reward cues. Results showing how NA-VP circuits
control motivation, and what neural activity signatures map on to increases and decreases in
motivation, will provide critical reference points for an understanding of how pathway-specific
changes in brain activity could contribute to excessive motivation in addictive behaviors. The
relative non-invasiveness of the procedure also carries translational potential for disrupting
severely excessive reactions to drug-associated stimuli.

## Key facts

- **NIH application ID:** 9975151
- **Project number:** 5R01DA044199-03
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Kyle S Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $502,243
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975151

## Citation

> US National Institutes of Health, RePORTER application 9975151, Brain Circuit Mechanisms for Reward Cue Attraction (5R01DA044199-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975151. Licensed CC0.

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