# Mesolimbic Circuit Function Underlying Individual Alcohol Drinking

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $44,436

## Abstract

PROJECT SUMMARY
Harmful alcohol use remains a serious public health issue, resulting in 3 million global deaths per year and
contributing to more than 200 disease and injury conditions. Within the United States, the prevalence of
Alcohol-use Disorder (AUD) has increased significantly, from 8.5% to 12.7% over the last 10 years and whose
complex etiology has limited the number of effective therapeutics currently available. An interesting
phenomenon in alcohol drinking is the variability of consumption occurring within the human population: some
individuals drink casually while others drink in an uncontrolled manner, escalating their consumption and
eventually developing alcohol dependence. To understand the circuit-specific functions underlying this
phenomenon of individual alcohol drinking variability, we utilized isogenic C57BL/6J mice, an inbred mouse
strain typically used to study alcohol-drinking behaviors. This mouse model provides the unique opportunity to
investigate the neurophysiological mechanisms underlying low and high alcohol drinking behaviors,
independent of genetics. Furthermore, it is known that a hallmark of the progression of AUD is the dysfunction
of dopamine (DA) neurons projecting from the ventral tegmental area to (VTA-NAc) the nucleus accumbens,
an area critical to encoding the salience of both drug and naturalistic stimuli. Using in vivo fiber photometry
calcium imaging and in vivo electrophysiological recordings, we are now able to determine the neural
population response of the VTA-NAc DA circuit before and after the establishment of alcohol drinking
phenotype, to illuminate the transition to healthy or unhealthy alcohol drinking profiles. Our preliminary data
show that the magnitude of the primary reinforcing VTA-NAc DA response to rewarding and salient stimuli
correlates with future establishment of alcohol preference (Aim 1). Further, alcohol-induced neuroadaptations
differentially affect naturalistic behaviors in mice, including exploration and response to reward, and cause
heightened or blunted responses to alcohol (Aim 2). By assessing the VTA-NAc DA neuronal profile of activity
during naturalistic mammalian behaviors prior to and after alcohol exposure, this project will provide novel
insight into physiological and real-time predictors of future, individual alcohol drinking and how alcohol actively
and reciprocally attenuates or exacerbates VTA-NAc DA circuit function, leading to subsequent maladaptive
behaviors.

## Key facts

- **NIH application ID:** 10231233
- **Project number:** 5F31AA028167-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Sarah Elizabeth Montgomery
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,436
- **Award type:** 5
- **Project period:** 2019-09-23 → 2022-09-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231233

## Citation

> US National Institutes of Health, RePORTER application 10231233, Mesolimbic Circuit Function Underlying Individual Alcohol Drinking (5F31AA028167-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10231233. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*