Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Serotonin and dopamine dynamics during kappa opioid mediated aversion

Award Number: F31DA065365
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/16/2026
PERIOD OF PERFORMANCE END DATE: 03/15/2029

Group Awards By:

View Award Description

Serotonin and dopamine dynamics during kappa opioid mediated aversion - PROJECT SUMMARY/ NARRATIVE Substance use disorder affects about 24 million people in the US due to the heightened availability of psychostimulants and synthetic opioids. Drug overdose deaths have also dramatically increased, requiring an urgent need to develop new therapeutics for this ongoing epidemic. Identifying how stress increases vulnerability to the reinforcing effects of drugs in susceptible individuals is important for developing effective strategies to treat SUD and mood disorders. Stress activates the release of the endogenous neuropeptide dynorphin (Dyn) that activates Gαi/o -coupled Kappa opioid receptor (KOR). Activation of KOR leads to the recruitment of the mitogen- activated protein kinase (MAPK), specifically p38α in addition to its canonical Gαi/o·Gβγ activity. KOR activation of p38α in serotonergic neurons (5HT) has been shown to mediate stress-induced potentiation of cocaine preference and increased serotonin transporter (SERT) function in the dorsal raphe nucleus (DRN). This increase in SERT activity is hypothesized to cause a hyposerotonergic state in the nucleus accumbens (NAc). In contrast, during morphine withdrawal, the hyposerotonergia is hypothesized to be a function of increased presynaptic inhibition of 5HT release by KOR. Thus, the mechanism by which KOR activation leads to hyposerotonergia remains to be resolved. Additionally, KOR activation of p38α in the ventral tegmental area (VTA) dopamine (DA) neurons is also required for aversion in mice, and pharmacological inhibition or selective gene deletion of p38α in VTA DA neurons blocks the aversive response to stress. Together, the Dyn/KOR system remains a potent modulator of both the 5HT and DA systems that regulate the stress response. Understanding how 5HT and DA dynamics are regulated by KOR/Dyn is an essential next step in the development of novel therapeutics for stress-induced mood disorders and SUD. Both Aims 1 and 2 of the proposal will characterize the pharmacological and behavioral role of stress-induced activation of Dyn/KOR/p38ɑ MAPK using in vivo fiber photometry with novel GRAB sensors and cell-specific CRISPR gene deletion to monitor real-time 5HT and DA tone in the NAc. These studies will be the first to offer high-resolution, simultaneous analysis of the 5HT/DA systems modulation during stress to describe 1) 5HT/DA sensitivity to p38α during both pharmacological and behavioral modulation, 2) the mechanism by which KOR G-biased agonists and antagonists may promote stress resilience, and 3) use dual-color imaging to understand 5HT/DA together during stress. These findings will provide foundational knowledge informing stress, neuropharmacology, and opioid fields.


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: 2026 ( Subtotal = $46,988 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	002	1	3/25/2026	NEW	$576
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	000	1	2/6/2026	NEW	$46,412
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Drug Use and Addiction Research Programs	001	1	2/6/2026	NEW	$0
														Subtotal = $46,988

Grand Total All Awards = $46,988

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Serotonin and dopamine dynamics during kappa opioid mediated aversion

Award Number: F31DA065365

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/16/2026

PERIOD OF PERFORMANCE END DATE: 03/15/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer