Tuesday, July 1, 2025 7/1/2025

DEFINING DYNORPHIN-CRF CIRCUITS IN STRESS AND NICOTINE BEHAVIORS

Award Number: R00DA038725
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2021

Group Awards By:

View Award Description

DEFINING DYNORPHIN-CRF CIRCUITS IN STRESS AND NICOTINE BEHAVIORS - DESCRIPTION (provided by applicant): The overall goal of this research is to better understand role of dynorphin and CRF in negative affective behaviors that are associated with nicotine withdrawal. Both dynorphin and CRF systems have been shown to drive stress and aversive behaviors but few studies have determined how these systems modulate one another to drive these behaviors through the extended amygdala. Dynorphin/Kappa Opioid Receptor (KOR) activity has been known to mediate negative emotional states inducing, dysphoria, aversions, and depression. CRF also produces dysphoria, aversion and anxiety-like behavior via dynorphinergic interactions, and it has been hypothesized that the increased release of CRF may be a primary contributor in the development of anxiety disorders. Therefore, we propose to examine the role and interactions of CRF and dynorphin in the mediation of aversive behaviors and whether this in turn modulates nicotine withdrawal. This five-year project has three specific aims. In the first aim (during the K99 phase) we will determine whether dynorphin regulates aversion in the ventral NAc. The second aim (during the K99 phase) is to examine the mechanisms in which nicotine interacts with the dynorphin/kappa opioid system to regulate negative affective behaviors. Here we will determine whether stimulation of dynorphin containing neurons in the NAc mediates aversion and withdrawal behavior and whether this is KOR-dependent. In these aims we will quantify dynorphin release in the NAc following optogenetic stimulation. During the R00 independent phase (Aim 3) we will quantify dynorphin release in the NAc before and following chronic nicotine exposure. We will also optogenetically stimulate CeA- CRF containing neurons and measure dynorphin release in the NAc, to examine whether CRF regulates dynorphin release and behavior characteristic of withdrawal. Since, both CRF and dynorphin are involved in the stress response and preliminary data has shown that chronic stress can block KOR-induced drug seeking, we will also determine the role of CRF1-R/KOR interactions in reinstatement of nicotine seeking, following exposure to stress. Together this work has important therapeutic implications as it will enhance our understanding of dynorphin/CRF cell-types, neural circuits that modulate negative affective behaviors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	UNIVERSITY OF HEALTH SCIENCES AND PHARMACY IN ST. LOUIS	1 PHARMACY PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Drug Use and Addiction Research Programs	000	5	5/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $249,000 )
2019	2019	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Drug Use and Addiction Research Programs	000	5	8/13/2019	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2018 ( Subtotal = $249,000 )
2018	2018	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Drug Use and Addiction Research Programs	000	4	8/17/2018	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2017 ( Subtotal = $249,000 )
2017	2017	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Drug Use and Addiction Research Programs	000	3	8/23/2017	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $747,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

DEFINING DYNORPHIN-CRF CIRCUITS IN STRESS AND NICOTINE BEHAVIORS

Award Number: R00DA038725

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2021

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer