# Electrophysiology of alcohol in extended amygdala

> **NIH NIH U01** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $669,844

## Abstract

This is a competitive U01 renewal application under the Integrative Neuroscience Initiative on Alcoholism-
Neuroimmune (INIA-N) consortium (Notice# RFA-AA-16-004/5/6) to identify the role of immune signaling in
ethanol dependence and develop new therapeutic strategies for the treatment of alcoholism. This U01
component will provide critical information on cellular mechanisms and neurobiological targets to other INIA-
N investigators to bridge alcohol basic research with the human condition.
Genetic evidence from INIA-N indicates that immune-related pathways, including interleukin-1β (IL-1β) and
IL-10, are altered in alcohol dependence. Our recent results show that cytokines strongly influence neuronal
function by modulating GABA neurotransmission in the central amygdala (CeA), a brain region involved in
excessive drinking and ethanol dependence. The medial prefrontal cortex (mPFC) is also involved in the
development of ethanol dependence and displays differences in its immune responses to chronic alcohol
treatment; a stronger immune response is elicited in the cortex compared with the CeA. Our hypothesis is
that alcohol exposure dysregulates neuroimmune mechanisms, leading to a general upregulation of
proinflammatory elements and downregulation of antiinflammatory elements that contribute to altered
synaptic transmission and alcohol-related behaviors. Thus, in this renewal, in addition to the focus on
proinflammatory elements (such as IL-1β) we will investigate antiinflammatory systems (IL-10, IL-1ra) in the
CeA and mPFC. In Aim 1 and 2, to induce ethanol dependence, we will use the chronic intermittent
ethanol–two-bottle choice (CIE-2BC) paradigm in both male and female mice. We will apply behavioral,
biochemical, and electrophysiological approaches to characterize dysregulation of the pro- and
antiinflammatory mechanisms in alcohol-drinking animals. Aim 3 will provide behavioral and
electrophysiological testing of the effects of ethanol-induced neuroimmune responses on physiological
functions across species (rodents and nonhuman primates) and cellular and molecular mechanisms of the
candidate drugs that are identified by other INIA-N projects in selected animal models. Thus, we anticipate
that our studies will identify the role and mechanisms of action of neuroimmune factors in excessive alcohol
drinking. Our collaborations with the other INIA-N PIs will promote replicability and translational aspects of
our studies by testing our key targets in multiple species using multiple complementary approaches.
The key personnel involved in this proposal possess all of the necessary expertise to accomplish this
multidisciplinary program. Drs. M. Roberto and M. Bajo will be dedicated to the electrophysiology and
biochemical studies, and Dr. A. Roberts will perform the behavioral studies. These key personnel each have
extensive publication histories in their respective areas of expertise and ongoing collaborative interactions
with many other INIA PIs that...

## Key facts

- **NIH application ID:** 9853691
- **Project number:** 5U01AA013498-19
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** MARISA ROBERTO
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $669,844
- **Award type:** 5
- **Project period:** 2001-09-27 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853691

## Citation

> US National Institutes of Health, RePORTER application 9853691, Electrophysiology of alcohol in extended amygdala (5U01AA013498-19). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853691. Licensed CC0.

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