# Pituitary adenylate cyclase-activating polypeptide 27 in the paraventricular thalamus and its projections: Role in ethanol drinking

> **NIH NIH R01** · DREXEL UNIVERSITY · 2020 · $340,700

## Abstract

PROJECT SUMMARY
The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has previously been shown
through genetic knockout to suppress ethanol intake, but the brain regions and protein isoforms through which
this occurs remain to be identified. While the more highly expressed of the two PACAP isoforms, PACAP38, is
found to affect a range of behaviors, including anxiety and depression, our recent studies focus attention on
the more selectively-expressed PACAP27, which appears to have few such associations. We have found
PACAP27 to be significantly more dense than PACAP38 in neurons of a key node of the limbic system, the
paraventricular nucleus of the thalamus (PVT), which has a major role in pharmacologically-relevant ethanol
drinking. Moreover, these PACAP27-containing neurons are particularly dense in the posterior (p) subregion of
the PVT, and we have previously shown that activation of the pPVT can decrease ethanol drinking. Thus,
building on published and preliminary results, we hypothesize that PACAP27 in neurons of the PVT,
specifically in the pPVT, suppresses ethanol intake (Aim 1); and these effects are exerted through PACAP27
projections to the nucleus accumbens shell (NAcSh) (Aim 2). To test this, Aim 1 investigates the specific
hypothesis that expression of PACAP in cells of the pPVT functions to inhibit ethanol drinking, with minimal
effects on anxiety- and depressive-like behavior. To accomplish this, the proposed experiments will use an
overexpression AAV or an shRNA silencing AAV approach to (1) determine the effects of increasing PACAP
expression in the pPVT on ethanol drinking, (2) assess the effects of decreasing endogenous PACAP
expression in the pPVT on ethanol drinking, and (3) investigate the effects of increasing PACAP expression in
the pPVT on emotional behavior. Next, Aim 2 investigates the hypothesis that PACAP27 from the pPVT
suppresses ethanol drinking through projections to the NAcSh. Thus, the proposed experiments will use
anatomical, immunohistochemical, pharmacological, and chemogenetic techniques, to (1) identify the primary
projections of PACAP27 from the pPVT, (2) determine the effects on ethanol intake of PACAP agonists and
antagonists in the major projection region(s), and (3) establish if the effects of PACAP27 on ethanol intake are
due to direct projections from the pPVT. Together, these proposed studies should benefit public health by
offering insight into an understudied peptide isoform with few known behavioral effects, which could ultimately
lead to innovative drug therapies for treating alcohol use disorder.

## Key facts

- **NIH application ID:** 9941916
- **Project number:** 1R01AA028218-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Jessica Rose Barson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,700
- **Award type:** 1
- **Project period:** 2020-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941916

## Citation

> US National Institutes of Health, RePORTER application 9941916, Pituitary adenylate cyclase-activating polypeptide 27 in the paraventricular thalamus and its projections: Role in ethanol drinking (1R01AA028218-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9941916. Licensed CC0.

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