# Role of Kappa Opioid Receptors in Maladaptive Catecholamine Responses to Stress and Alcohol Exposure

> **NIH NIH U01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $348,750

## Abstract

Stress is a well-known factor in promoting heavy drinking and relapse to drinking in alcoholics, and
avoidance of the negative affective symptoms of ethanol withdrawal (e.g. anxiety) is also believed to play a
critical role in relapse to heavy ethanol use. Further, anxiety disorders may predispose individuals to drink
heavily and these high intakes may exacerbate the interaction of heavy drinking and anxiety. Negative affective
behaviors are modulated by neuropeptides such as dynorphin, and its target, kappa opioid receptors (KORs).
We will use a mouse model of chronic intermittent ethanol (CIE) exposure combined with forced swim stress to
understand the role that KORs play in the maladaptive neurobiological changes induced by stress/ethanol
interactions. Our previous work revealed that the function of the dynorphin/KOR system in the nucleus
accumbens (NAc) was robustly up-regulated by chronic ethanol exposure and withdrawal in a time/exposure
dependent manner in both the CIE model in mice and in a long-term voluntary ethanol drinking model in
monkeys. In addition, in mice we found that systemic administration of a KOR antagonist reduced
anxiety/compulsive behaviors (marble burying) and withdrawal-induced excessive drinking. Because
norepinephrine (NE) and dopamine (DA) are both involved in negative affective responses to stress, and are
known targets of KOR activity, we will examine KOR regulation of DA signaling in the NAc, which regulates
motivation to drink alcohol, and NE signaling in the basolateral amygdala (BLA), which regulates
stress/anxiety-related behaviors. We have established that KOR inhibition of DA signaling in the NAc is up-
regulated by chronic intermittent ethanol (CIE) exposure, and we will expand these findings to include
activation of the NE system by forced swim stress (FSS) and CIE, regulation of this system by KORs, and
interactions with DA that may exacerbate negative affective responses and subsequent ethanol drinking. The
overall goal is to define FSS and CIE-induced adaptations in stress-responsive limbic circuitry nodes that are
responsible for withdrawal-associated negative affect and that can be targeted for the treatment of alcoholism.

## Key facts

- **NIH application ID:** 9878034
- **Project number:** 5U01AA014091-18
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SARA RAULERSON JONES
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2003-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878034

## Citation

> US National Institutes of Health, RePORTER application 9878034, Role of Kappa Opioid Receptors in Maladaptive Catecholamine Responses to Stress and Alcohol Exposure (5U01AA014091-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9878034. Licensed CC0.

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