# Probing Cortical-nigral Dynophinergic Circuits in Alcohol Abuse

> **NIH NIH P60** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $265,116

## Abstract

Abstract
Excessive drinking cost the United States $249 billion in 2010 with 77% attributed to lost productivity, health
care costs, and accidents as a result of binge drinking. Despite this high cost, the precise neural mechanisms
that underlie escalated drinking remain elusive. The intermittent access (IA) paradigm is a rodent schedule of
alcohol drinking that reliably leads to voluntary escalated alcohol intake and preference as well as dysregulated
emotional behavior. While numerous neurochemical systems have been identified as playing a role in alcohol-
related behavioral pathology, one of the most promising leads for treatment is the Kappa Opioid Receptor
(KOR) and its endogenous ligand Dynorphin (Dyn). Consistent with the important role of this system in
excessive alcohol drinking, we found that pharmacological blockade of KOR leads to a suppression of
escalated IA drinking. Following IA, we found that dynorphin expressing neurons in the Insular Cortex show
evidence of increased recruitment. Further, we found that Dyn containing neurons in the Insular Cortex (ICDyn)
project to the Substantia Nigra (SN). Taken together, these preliminary data suggest that KOR signaling in the
the IC to SN pathway plays a key role in alcohol abuse, potentially via regulation of dysphoric behavioral
states. In this proposal we will use a strong multidisciplinary approach to test central hypothesis: Intermittent
access to alcohol causes dysregulation of Dyn / KOR systems in the insular cortex to substantia nigra
circuit that drive increased ethanol consumption.

## Key facts

- **NIH application ID:** 10078811
- **Project number:** 5P60AA011605-24
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Thomas L. Kash
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $265,116
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078811

## Citation

> US National Institutes of Health, RePORTER application 10078811, Probing Cortical-nigral Dynophinergic Circuits in Alcohol Abuse (5P60AA011605-24). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10078811. Licensed CC0.

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