# The Role of the Bed Nucleus of the Stria Terminalis-Norepinephrine System in Amphetamine-type Stimulant Use Disorders

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $669,826

## Abstract

PROJECT SUMMARY/ABSTRACT
 Amphetamine-type stimulants (ATS), such as methamphetamine (METH) are highly addictive and are the
second most used illicit drugs in the world. Even though ATS production in the US has dramatically increased
and stimulant use remain an important public health, financial, and legal issue, there are no proven
pharmacotherapies to treat ATS use disorders (AUD) due to a limited understanding of the brain circuits
underlying AUD and their complex mechanisms of action. Although many ATS increase both brain
norepinephrine (NE) and dopamine (DA), and have higher affinities for the NE transporter (NET) than the DA
transporter, far less attention has been paid to the role of central NE circuits as a potential target for treatment
of AUD. Recent preclinical and clinical studies have highlighted NE in the bed nucleus of the stria terminalis
(BNST) as an important contributor to substance abuse, withdrawal, and stress-induced reinstatement of drug
seeking. NE transmission in the ventral (v)BNST, which primarily originates from the nucleus of the solitary
tract (NST), integrates information from reward and stress related stimuli and mediates subsequent behavioral
responses. However, little is known about how the NST-NE vBNST pathway is implicated in AUD and how it
contributes to behavioral changes due to methodological limitations in selectively studying NE in the
anatomically small/complex and neurochemically heterogeneous BNST. Furthermore, the BNST is sexually
dimorphic and much smaller in volume (2.5X less for humans) in females than males, yet little is known about
sex differences in the NST-NE vBNST system and its effect on AUD.
 Aim 1 of this proposal will (i) identify anatomical and neurochemical differences in the NST-NEvBNST
system between male and female rats and (ii) characterize the effects of METH on NE regulation in the NST
and vBNST and the correlation of the NE system with stress-induced behavioral changes. Aim 2 will determine
the functional role of the NST-NEvBNST pathway in animal models of stress-induced METH seeking
(relapse/craving) by chemogenetically modulating this pathway in METH self-administration paradigms.
 To achieve these Aims, we propose an innovative and integrative approach utilizing fast-scan cyclic
voltammetry and chemogenetic modulation of NST-NE projection neurons to the vBNST in wild-type rats. This
study will fill an important gap in our understanding of the NST-NEvBNST pathway and its contributions to
the chronic effects of METH-induced neurochemical and behavioral changes and its distinct sex differences.
These results will provide insight into the underlying neurobiological mechanisms of ATS use and may lead to
novel therapeutics for of AUD using sex specific treatment strategies.

## Key facts

- **NIH application ID:** 10930024
- **Project number:** 5R01DA056547-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Jinwoo Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $669,826
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930024

## Citation

> US National Institutes of Health, RePORTER application 10930024, The Role of the Bed Nucleus of the Stria Terminalis-Norepinephrine System in Amphetamine-type Stimulant Use Disorders (5R01DA056547-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10930024. Licensed CC0.

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