# Connectomics of relapse to aggression seeking

> **NIH NIH R00** · UNIVERSITY OF WASHINGTON · 2020 · $245,445

## Abstract

Project Summary
 There is an increased risk for abnormal social behavior in individuals suffering from psychiatric disorders.
This is highlighted by the common comorbidity between aggression and addiction to opioids and other drugs.
One form of aggression in particular – appetitive aggression – exhibits symptomatology that closely mimics
drug addiction, and it is hypothesized that appetitive aggression is due to dysregulation of reward circuits in a
manner akin to drug addiction. This is an unproven hypothesis, and in contrast to drug addiction, the circuits
underlying motivational components of aggressive behavior in rodent models are largely unknown. Therefore,
the aim of this proposal is to obtain the necessary training to identify, interrogate, and manipulate mechanisms
underlying relapse to aggression seeking. It will also determine the effect of opioid dependence on relapse to
aggression seeking.
 This proposal will focus first on identifying the intact whole brain functional connectome of relapse to
aggression seeking, and then more specifically address the role of the nucleus accumbens (NAc) and its
afferent projections. The choice of this brain region is based on converging preliminary data implicating a
critical role for NAc in aggression reward, and NAc’s well established role as a critical locus regulating drug
addiction. This will be achieved using a novel behavioral model of aggression self-administration and relapse.
The functional and structural connectome will be identified using iDisco+, a whole brain clearing method, in
conjunction with viral retrograde tracing and Fos (a marker of neuronal activity) immunohistochemistry.
Because of the limited temporal resolution of Fos during learned behaviors, awake-behaving single-unit
electrophysiological recording will be used to observe how NAc neurons encodes aggression reward. Next, the
causal significance of the NAc and its afferent projections will be examined using region, circuit, and cell-type
specific chemogenetic manipulations. Lastly, this proposal will study the effect of oxycodone (a commonly
abused prescription opioid) dependence on relapse to aggression seeking, towards identification of novel
therapeutic interventions for the treatment of aggression comorbid with opioid addiction.

## Key facts

- **NIH application ID:** 9985782
- **Project number:** 5R00DA045662-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sam Golden
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,445
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985782

## Citation

> US National Institutes of Health, RePORTER application 9985782, Connectomics of relapse to aggression seeking (5R00DA045662-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9985782. Licensed CC0.

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