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

Identifying the behavioral and neural markers of opioid withdrawal induced risk taking and their relationship with relapse vulnerability.

Award Number: K99DA064776
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

Group Awards By:

View Award Description

Identifying the behavioral and neural markers of opioid withdrawal induced risk taking and their relationship with relapse vulnerability. - Project Summary Synthetic opioids, primarily fentanyl, are the leading cause of lethal overdoses in the US (>80,000/yr), with deaths rising 7.5-fold in the past decade. A major contributor to these deaths is relapse after detoxification, likely through reduced tolerance. While the causes of relapses are not fully understood, long-lasting cognitive symptoms of opioid withdrawal (OW) are proposed factors. Studying the impact of OW on cognition is challenging in clinical settings as many patients quickly relapse and baseline performances are critically unknown. To help guide causal answers, it is necessary to establish a translatable rodent model of OW to explore the development and progression of cognitive factors linked to relapse. To address this, Aim 1 (K99) proposes validating the rat Iowa Gambling Task (IGT) to explore OW-induced risky decision-making, as seen in abstinent opioid users performing the clinical IGT. Importantly, IGT scores in the clinic predict relapse, making its preclinical analog appropriate to explore shared neurobiological processes between cognition and relapse vulnerability during OW. The nucleus accumbens core (NAcc) is a striatal region that processes responses to rewarding and aversive stimuli via dopamine (DA) activity, and contributes to both risk-taking and opioid addiction. Within the NAcc medium spiny neuron (MSN) output cells expressing DA-D2 receptors (D2R) guide safe decision-making under conditions of risk, and their activation is strongly associated with relapse behaviors. However, no study has explored if NAcc D2R-MSNs represent a shared neural process driving risky behavior and relapse vulnerability during OW. These critical gaps will be addressed in Aims 2 (K99) and 3 (R00) where fiber photometry will be utilized to measure the dynamic in vivo activity of NAcc D2R-MSNs in rats trained to self-administer fentanyl and perform the IGT under OW conditions. The efficacy of standard opioid maintenance treatment (buprenorphine) on behavioral and neurobiological consequences of OW will also be tested in Aim 3. Collectively, findings will advance the field by informing the development and progression of OW-induced cognitive deficits, determining region- and cell-specific contributions to such behavior, and defining the relationship between these behavioral and neural signatures and the likelihood of subsequent relapse behavior. The K99 mentored phase experiments will provide training for the candidate to independently measure translatable cognitive behavior through training with Dr. Jared Young (mentor), while simultaneously testing in vivo cell activity via fiber photometry, through training with Dr. Samuel Barnes (co-mentor). Dr. Giordano de Guglielmo (co-mentor) will provide further training in the use of preclinical models of drug-taking and drug- seeking behaviors to carry out the proposed experiments and to guide data interpretations given their expertise in addiction medicine. Alongside the candidate’s already strong knowledge of preclinical models of behavior and addiction, and their technical skills in pharmacology research and design, the proposed work will provide a strong setup with the intent to independently operate their own research laboratory in the addiction neuroscience field.


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 = $165,669 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	1	7/16/2026	NEW	$165,669
														Subtotal = $165,669

Grand Total All Awards = $165,669

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identifying the behavioral and neural markers of opioid withdrawal induced risk taking and their relationship with relapse vulnerability.

Award Number: K99DA064776

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer