# Identification of novel mechanisms in alcohol-induced cognitive dysfunction

> **NIH NIH R00** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $249,000

## Abstract

Project Summary
Impairments in cognitive function are among the “hallmark” characteristics of addiction. In this regard, alcoholism
is associated with dysfunction of multiple cognitive faculties that may underlie the difficulties in reversing alcohol-
seeking behaviors during extended periods of abstinence. Repeated cycles of alcohol intoxication and
withdrawal dysregulate brain amino acid systems, an effect that is thought to impart a hyperexcitable state.
Whereas acute withdrawal mobilizes signaling of the primary excitatory neurotransmitter glutamate, over time
these neurological disturbances subside. The emergence of cognitive disruptions during protracted withdrawal
suggests an underlying dysfunction in the medial prefrontal cortex (mPFC). In this regard, drugs of abuse
mobilize protein kinases that, over the course of repeated exposures, produce long-term changes in synaptic
function and molecular signaling networks that coincide with addictive phenotypes. We propose that withdrawal-
induced cognitive impairments relate to an undercurrent of dysfunctional kinase signaling pathways that preserve
aberrant glutamate receptor signaling in discrete regions of the mPFC. To this end, the K99 phase will involve
training in novel proteomic enrichment strategies to broadly evaluate the mPFC proteome, as isolated by dorsal
and ventral regions, towards the goal of identifying novel protein signaling targets in alcohol-dependent rats
experiencing protracted withdrawal. We will then seek to characterize the molecular and cognitive behavioral
relevance of these targets throughout the R00 phase using novel peptidomimetic strategies that target the
disruption of specific protein-protein interactions. This study will provide novel insight into distinct signaling
pathways that underlie alcohol-induced cognitive dysfunction.

## Key facts

- **NIH application ID:** 10088146
- **Project number:** 4R00AA025393-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** LUIS ALBERTO NATIVIDAD
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088146

## Citation

> US National Institutes of Health, RePORTER application 10088146, Identification of novel mechanisms in alcohol-induced cognitive dysfunction (4R00AA025393-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10088146. Licensed CC0.

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