# Role of prelimbic input to the rostromedial tegmental nucleus in encoding sensitivity to the aversive properties of ethanol

> **NIH NIH F32** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $69,080

## Abstract

PROJECT SUMMARY
An individual’s subjective response to alcohol’s rewarding and aversive properties contribute to their risk for
developing alcohol use disorder (AUD). For example, individuals who are less sensitive to the aversive properties
of alcohol, which typically limit drinking, are more likely to drink heavily and develop AUD. Conditioned taste
aversion (CTA) is an assay that allows preclinical researchers to probe sensitivity to the aversive properties of
drugs. Using this assay, our preliminary data reveal the presence of significant individual differences in sensitivity
to the aversive properties of ethanol similar to that which is observed in clinical populations. Specifically, some
individuals exhibit strong ethanol-induced CTA (CTA-sensitive), whereas others exhibit minimal CTA to ethanol
(CTA-resistant). Despite strong evidence for a relationship between subjective response to ethanol and risk for
AUD, the neurobiological substrates that encode sensitivity to ethanol’s aversive properties are poorly
understood. Recent work from our lab suggests that the rostromedial tegmental nucleus (RMTg) signals the
aversive properties of ethanol. The neural circuits driving engagement of the RMTg to signal ethanol aversion
are unknown, but data from our lab point toward the prelimbic (PL) subdivision of the medial prefrontal cortex as
a potential source. The PL and RMTg are both implicated in the behavioral response to aversive stimuli, and we
have discovered that the PL sends dense projections to the RMTg. We also found that this projection is activated
during exposure to aversive stimuli, and that stimulation of this circuit drives avoidance. Together, this leads us
to hypothesize that RMTg-projecting PL neurons encode sensitivity to the aversive properties of ethanol and that
differences in circuit activity contribute to individual differences in subjective response to ethanol. We will test
this hypothesis across three specific aims. In Aim 1, we will combine CTA with in vivo fiber photometry to compare
PL-RMTg activity in CTA-sensitive and -resistant individuals. In Aim 2, we will use whole-cell patch-clamp
electrophysiology to examine differences in the physiology of RMTg-projecting PL neurons across CTA
phenotypes. In Aim 3, we will conduct whole-genome RNA-sequencing in RMTg-projecting PL neurons to assess
translational differences in CTA-sensitive and -resistant individuals. Together, these experiments will provide
new mechanistic insight into the neurobiology underlying sensitivity to ethanol’s aversive properties, while also
providing the applicant with new training in conceptually innovative and cutting-edge approaches in neuroscience
research.

## Key facts

- **NIH application ID:** 10749662
- **Project number:** 1F32AA031166-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Kathryn Przybysz
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $69,080
- **Award type:** 1
- **Project period:** 2023-12-15 → 2024-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749662

## Citation

> US National Institutes of Health, RePORTER application 10749662, Role of prelimbic input to the rostromedial tegmental nucleus in encoding sensitivity to the aversive properties of ethanol (1F32AA031166-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10749662. Licensed CC0.

---

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