# Behavioral Neurobiology of Aggression, Alcohol, GABA, and 5-HT

> **NIH NIH R01** · TUFTS UNIVERSITY MEDFORD · 2020 · $351,738

## Abstract

Project Summary
Alcohol plays a key role in at least half of all violent assaults, incidents of domestic violence, homicides
and murders. However, the neural and behavioral processes underlying the link between alcohol and
violence remain poorly understood. This research proposal aims to delineate the neural mechanisms by
which alcohol persistently escalates the motivation to commit intense aggressive acts in some
individuals. These aims are empirically pursued using a fixed interval (FI) schedule of operant
responding which will be reinforced by the opportunity to engage in an aggressive encounter, allowing
us to directly quantify aggressive motivation. Here, the role of corticotropin-releasing factor (CRF) in
both (1) the motivation to engage in aggressive acts, and (2) the performance of aggressive behaviors
will be quantitatively and qualitatively examined. By isolating the motivation to engage in aggression,
we will be able to identify the underlying neural mechanisms that relate to subsequent aggressive
behaviors. The overarching hypothesis is that escalated aggression, particularly when engendered by
repeated exposures to alcohol, is a function of dysregulated CRF-modulated neurocircuits, namely the
hypothalamus-ventral tegmental area (VTA) and hypothalamus-dorsal raphé nucleus (DRN) pathways.
These circuits may be fundamental to the modulation of emotional processing via dopaminergic and
serotonergic systems, respectively. In a specific subset of individuals, we predict that subpopulations of
CRF neurons contribute to escalated motivation to seek out aggressive opportunities after alcohol
consumption. In the first aim, we plan to fully characterize the enduring nature of alcohol-escalated
aggressive motivation as a function of alcohol dose and as it relates to the duration since alcohol
consumption. Aim two will use cellular and molecular tools to investigate plasticity in neuropeptidergic
mechanisms that contribute to the persistent escalation of aggressive motivation after repeated alcohol
intake. This work will reveal changes in overlapping, intersecting or parallel CRF mechanisms that
ultimately converge on dopaminergic and serotonergic systems that are critical for emotional
processing. We will also use transgenic technology to define the relative importance of CRF-expressing
cell populations in hypothalamus-VTA and hypothalamus–DRN circuits. The proposed experimental
work portrays highly translational and ethologically valid analyses of species-normative and escalated
forms of aggression engendered by alcohol. Novel targets for therapeutic interventions are anticipated
based on the results of these studies.

## Key facts

- **NIH application ID:** 9985676
- **Project number:** 5R01AA013983-18
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** KLAUS A MICZEK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,738
- **Award type:** 5
- **Project period:** 2003-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985676

## Citation

> US National Institutes of Health, RePORTER application 9985676, Behavioral Neurobiology of Aggression, Alcohol, GABA, and 5-HT (5R01AA013983-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985676. Licensed CC0.

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