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

Dopamine receptor type 2 (D2)-expressing cells in the ventral hippocampus controlrelapse behavior

Award Number: K99DA065809
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

Group Awards By:

View Award Description

Dopamine receptor type 2 (D2)-expressing cells in the ventral hippocampus controlrelapse behavior - Substance use disorders (SUDs) have surged in prevalence, with cocaine-related overdose deaths disproportionately affecting marginalized populations. Dysfunctional dopamine (DA) signaling has been tied to SUD, with extensive research into DA signaling within mesocorticolimbic circuits specifically focused on the striatum. However, no FDA-approved pharmacotherapies exist for cocaine use disorder, highlighting the urgent need for novel targets. Recent evidence implicates the ventral hippocampus (vHPC) in drug-seeking behaviors and our lab has validated that the vHPC exhibits dopamine-sensing populations of cells that expression the DA receptor type 1 (D1) and type 2 (D2). My findings reveal that vHPC D2 cells drive reinforcement and voluntary drug taking through mechanisms that remain poorly understood. This K99/R00 proposal aims to elucidate how vHPC D2 neuron activity and molecular signaling contribute to cocaine relapse vulnerability. In Aim 1, I will characterize the activity of vHPC D2 neurons during cocaine intravenous self-administration (IVSA), extinction, and cue-induced reinstatement using one-photon calcium imaging. Chemogenetic manipulation will establish the causal role of these neurons in relapse, testing the hypothesis that their activation predicts and intensifies relapse susceptibility. In Aim 2, I will investigate transcriptomic changes in vHPC D2 neurons following cue-induced reinstatement using single-nucleus RNA sequencing (snRNA-seq). Weighted gene co- expression network analysis (WGCNA) will identify molecular pathways that drive relapse vulnerability, with validation through RNA-scope and behavioral correlation. In Aim 3, I will explore how endocannabinoid (eCB) signaling regulates vHPC D2 neuron activity using CRISPR-mediated knockdown of cannabinoid receptor type 1 (CB1R). These data could reveal distinct cocaine-induced changes in function or transcriptome which could provide insight into potential biomarkers making individuals more susceptible to the reinforcing effects of drugs of abuse, and thus addiction liability. Through these novel findings, we will expand our understanding of how drugs of abuse cause molecular, neural, and circuit changes in the brain to hijack reward circuitry and lead to maladaptive reward processing, cue-outcome associations, and drug seeking/taking behavior characteristic of SUD and potentially reveal new biomarkers that could predict SUD susceptibility.


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 = $181,092 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	1	4/21/2026	NEW	$181,092
														Subtotal = $181,092

Grand Total All Awards = $181,092

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Dopamine receptor type 2 (D2)-expressing cells in the ventral hippocampus controlrelapse behavior

Award Number: K99DA065809

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer