# The Role of Kappa-Opioid Receptors in Alcohol Use Disorders

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2020 · $339,634

## Abstract

Project Summary. A fundamental characteristic of alcohol use disorders is the loss of control over alcohol
consumption that results in progressively escalating levels of alcohol use and facilitates the progression to
alcohol-dependence. Given the comorbidity of alcohol dependence and disorders of affect such as de-pression
is extremely high, it has been posited that self-medication of negative affective states contributes to continued
excessive alcohol use and relapse. Furthermore, negative affective states produced by chronic alcohol
exposure can influence the neurocircuitry of cognitive control systems to perpetuate further excessive alcohol
use. Once that degree of dysregulation is reached, components of the dependence cycle serve to facilitate each
other in a manner that is extremely deleterious to personal, familial and societal welfare. The principal
investigator’s long-term goal is to identify effective therapeutic targets and strategies for the treatment of
AUDs. The objective of this renewal application, which is the next step in pursuit of that goal, is to understand
the neuroadaptations in dynorphin (DYN) / kappa-opioid receptor (KOR) systems that occur in response to
chronic alcohol exposure and contribute to maladaptive behavioral regulation in the form of maladaptive
behavioral regulation. The central hypothesis is that the DYN / KOR system becomes progressively
dysregulated in a manner that promotes the continued excessive consumption of alcohol and perpetuates the
cycle of alcohol dependence. The rationale for the proposed studies is that identification of novel DYN / KOR-
related treatment targets will enable the development of effective therapies designed to alleviate maladaptive
behavioral regulation produced by dysphoria and alcohol dependence. This hypothesis will be tested by
pursuing the following specific aims: Aim #1 evaluates kappa-opioid receptor dysregulation within cortical
nuclei during acute withdrawal within working memory and impulse control domains. Aim #2 assesses the
role of KORs in amygdalar nuclei in response to non-dependent dysphoria cues and alcohol-dependent
withdrawal cue-induced maladaptive behavioral regulation using a combination of pharmacological and
inducible genetic approaches. Animal models of self-administration, negative affective-like behavior, working
memory and impulse control will serve as functional end-points to systematically investigate the mechanisms
that contribute to maladaptive behavioral regulation in AUDs. These specific aims will collectively help to
identify important neuroadaptations in DYN / KOR systems that can promote the transition to, and
perpetuation of, AUDs and will provide much needed information regarding the influence of DYN / KORs on
the neurocircuitry maladaptive behavioral regulation. Such a contribution is significant because it will help
develop personalized therapeutic targets to treat AUDs that focus on the removal of maladaptive phenotypes;
a strategy that sh...

## Key facts

- **NIH application ID:** 9999385
- **Project number:** 5R01AA020394-10
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Brendan M Walker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,634
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999385

## Citation

> US National Institutes of Health, RePORTER application 9999385, The Role of Kappa-Opioid Receptors in Alcohol Use Disorders (5R01AA020394-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999385. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*