# Rat Animal Models & Drug and Gene Testing Core (RAM-DGTC)

> **NIH NIH U24** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $373,601

## Abstract

According to the Centers for Disease Control and Prevention (CDC), alcohol use disorder (AUD) continues to
be the third leading cause of death in the U.S. Multiple studies from the Collaborative Studies on Genetics of
Alcoholism (COGA) and Study of Addiction: Genes and Environment (SAGE) confirm that being an individual
with a family history positive (FHP) for alcoholism is a key, predictable determinant for the development and
expression of AUD. The selectively bred alcohol-preferring P rat and, to a lesser extent, the high-alcohol-
drinking HAD rat lines meet criteria put forth for a valid animal model of alcoholism and display certain genetic-,
behavioral-, and physiological-related phenotypes observed in FHP individuals. This core is a Research
Resource for the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune [INIA-N]) consortium.
The Specific Aims of this Research Resource will test the effects of (1) treatment with target small molecules
on excessive ethanol (EtOH) drinking by P and HAD rats, (2) infusions of shRNA and/or cDNA (to
downregulate or upregulate, respectively, target gene expression levels) into subregions of the extended
amygdala (Ext-Amyg) and medial prefrontal cortex (mPFC) on excessive EtOH drinking by P and HAD rats,
and (3) work closely with Dayne Mayfield’s, and others U01s, in identifying neuroimmune signaling, and/or their
pathway, targets associated with a genetic predisposition to develop AUD. For this, we will use our previous
and ongoing genomic and proteomic work for excessive alcohol drinking. Some of the targets observed so far
match those of INIA-N as a whole including toll-like receptors [TLRs], interleukin receptors [ILRs],
phosphodiesterase 4 [PDE4], and peroxisome proliferator-activated receptor [PPAR]. This core will work
closely with U01 components and the U24 “Electrophysiology Core” to address pertinent research questions
raised by respective U01s and/or the Administrative Core. This is a significant core that will provide important
verification and heuristic information on neuroimmune signaling in AUD in general, as well as in genetically
predisposed subjects in particular. Moreover, this Core will evaluate compounds suggested by Mayfield’s
LINCS analysis and manipulators of immune targets revealed in ongoing work of INIA-N. This is a highly
innovative project that uses state-of-the-art techniques to selectively alter the expression of “target” genes
within discrete CNS subregions in multigenerational, genetically selected (P, HAD1 and HAD2) FHP rats. This
U24 core provides synergy with a number of INIA-N investigators, including Blednov, Crabbe, Hitzemann,
Kieffer, Lasek, Mason, Mayfield, Morrisett, Pfefferbaum, and Roberto, as well as Becker/Lopez of INIA-Stress.

## Key facts

- **NIH application ID:** 9853699
- **Project number:** 5U24AA013522-19
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** RICHARD LOWELL BELL
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,601
- **Award type:** 5
- **Project period:** 2001-09-27 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853699

## Citation

> US National Institutes of Health, RePORTER application 9853699, Rat Animal Models & Drug and Gene Testing Core (RAM-DGTC) (5U24AA013522-19). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853699. Licensed CC0.

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