# Mechanisms underlying neuropeptide release in the extended amygdala

> **NIH VA I01** · DURHAM VA MEDICAL CENTER · 2020 · —

## Abstract

Although endogenous neuropeptide transmitters play critical roles in the reinforcing effects
of ethanol consumption and the aversive effects of ethanol withdrawal, we have a poor
understanding of mechanism(s) underlying central neuronal release of neuropeptides. This gap
in our knowledge critically undermines our abilities to elucidate the biological effects of ethanol
(EtOH), as 1) multiple studies have demonstrated that acute and chronic EtOH induces release
of neuropeptides in brain regions associated with EtOH reinforcement and withdrawal-induced
aversion, and 2) one of the very few medications (naltrexone) commonly used to treat EtOH
craving is assumed to act by antagonizing effects of endogenously-released opioid peptides.
Multiple behavioral studies document involvement of endogenous neuropeptides in response to
stress, drugs and other behavioral states, but we still know very little about the physiological
mechanisms underlying neuropeptide release. Howevever, this knowledge could significantly
enhance our ability to create novel pharmacotherapies for alcohol dependence.
 Previous studies from our lab and others have shown enhanced release of neuropeptides
in the central nucleus of the amygdala (CeA) by acute EtOH exposure. In addition, several studies
have shown persistent release of specific peptides following withdrawal from chronic intermittent
EtOH; these peptides may mediate the “anxious-like” withdrawal behaviors. However, our current
preliminary data suggest that many conventional notions of peptide release may be inaccurate or
incomplete; specifically, high-frequency activity is neither sufficient nor necessary for peptide
release. We have recently begun exploring potential cellular phenomena that could regulate
peptide release and our preliminary data demonstrate that we can relatively selectively induce
release of the neuropeptide corticotropin-releasing factor (CRF) using optogenetic methods. In
addition, we have characterized the potential role of the BK potassium channel in mediating EtOH
effects. Proteomic analysis has shown that the BK channel is linked to the intracellular enzyme
dynamin-1, a protein essential for mediating peptide release. We hypothesize that in contrast to
fast synaptic transmission at axonal terminals, central neuropeptide release is mediated by a
mechanism dependent on both the BK channel and dynamin-1.
 Because of the wealth of preclinical data implicating endogenous neuropeptides in effects
of ethanol consumption and the clinical experience with naltrexone (which acts by blocking effects
of endogenous opioid peptides), we believe that mechanistic studies of the physiological and
ethanol-induced release of peptides in the extended amygdala may facilitate development of
novel pharmacotherapies for the treatment of alcoholism.

## Key facts

- **NIH application ID:** 9898253
- **Project number:** 5I01BX001271-08
- **Recipient organization:** DURHAM VA MEDICAL CENTER
- **Principal Investigator:** Scott D. Moore
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-10-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898253

## Citation

> US National Institutes of Health, RePORTER application 9898253, Mechanisms underlying neuropeptide release in the extended amygdala (5I01BX001271-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898253. Licensed CC0.

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