# Dopaminergic Modulation of Excitatory Transmission in BNST and Regulation by Ethanol

> **NIH NIH F32** · VANDERBILT UNIVERSITY · 2020 · $33,723

## Abstract

Project Summary/Abstract
Alcohol addiction is characterized by repeated relapses to alcohol abuse despite negative consequences. This
counter-adaptive behavior is believed to result from adaptations in underlying neurocircuitry which occur in
response to chronic alcohol abuse. These adaptations result in persistent negative affective states, during
abstinence, which drive reinstatement of alcohol use as a means of negative reinforcement, or relief from
negative conditions. The bed nucleus of the stria terminalis (BNST) is a key mediator of stress and anxiety
states and behavioral responses to stressors. Models of stress-induced reinstatement of drug seeking have
identified norepinephrine signaling in the BNST as critical to relapse behavior. Noradrenergic excitation of the
BNST through β-adrenergic receptors promotes anxiety-like behaviors and drug reinstatement, whereas
inhibition of BNST activity through α2-adrenergic receptors reduces anxiety-like behaviors. The BNST also
receives prominent dopaminergic innervation from the ventral tegmental area (VTA). Investigations into the
role of dopaminergic signaling in the BNST are relatively sparse and somewhat contradictory. For example,
low doses of bath applied dopamine resulted in increased excitatory activity in the BNST, while high doses
resulted in increased inhibitory actions. Further, the inhibitory actions are suggested to occur through
dopamine cross-activation of α2-adrenergic receptors. In order to resolve these discrepancies, it is important
to have a clear understanding of endogenous dopamine signals and how rapid changes in dopamine
concentrations may selectively recruit post-synaptic receptor activation. Often, investigations of dopamine
signaling use fast-scan cyclic voltammetry, which provides high temporal resolution of dopamine release and
uptake in response to local electrical stimulation of terminals fields. However, in the BNST, dopamine and
norepinephrine provide overlapping innervation, thus both catecholamines are released in response to local
electrical stimulation, and cyclic voltammetry cannot distinguish between catecholamines. This hinders the use
of this technique in assessing the potentially opposing roles of dopamine and norepinephrine signaling on
BNST synaptic physiology. In this proposal we introduce a model in which we optogenetically target VTA
dopamine neurons projecting to the BNST, such that we may use selective optical-stimulation of local
dopamine release, measured with cyclic voltammetry, in BNST slices, ex vivo. Further, we propose to use
optically-stimulated dopamine release in combination with whole cell electrophysiology to measure the cellular
responses to endogenous dopamine signals. This ex vivo model allows us to employ various pharmacological
manipulations to assess how dopamine signaling is integrated into synaptic physiology and to what degree
endogenous dopamine signals recruit activation of α2-adrenergic receptors. Finally, we will examine how...

## Key facts

- **NIH application ID:** 10264772
- **Project number:** 5F32AA027409-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** James Melchior
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,723
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264772

## Citation

> US National Institutes of Health, RePORTER application 10264772, Dopaminergic Modulation of Excitatory Transmission in BNST and Regulation by Ethanol (5F32AA027409-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10264772. Licensed CC0.

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