Federal Project Grant Award Summary

Icahn School of Medicine at Mount Sinai received a $181,092 Project Grant from the National Institute on Drug Abuse under the Drug Use and Addiction Research Programs (CFDA 93.279) effective May 1, 2026, through April 30, 2028. This K99/R00 award funds research to elucidate the role of dopamine receptor type 2 (D2)-expressing cells in the ventral hippocampus in cocaine relapse behavior. The research addresses a critical gap in understanding substance use disorder mechanisms, as no FDA-approved pharmacotherapies currently exist for cocaine use disorder despite escalating cocaine-related overdose deaths, particularly among marginalized populations.

The grant supports three coordinated research aims focused on characterizing ventral hippocampus D2 neuron activity and molecular signaling during cocaine self-administration and relapse. Aim 1 employs one-photon calcium imaging and chemogenetic manipulation to establish the causal relationship between D2 neuron activation and relapse susceptibility. Aim 2 utilizes single-nucleus RNA sequencing and weighted gene co-expression network analysis to identify molecular pathways driving relapse vulnerability. Aim 3 investigates endocannabinoid signaling regulation through CRISPR-mediated knockdown of cannabinoid receptor type 1. The research deliverables include empirical findings on neural circuit mechanisms, transcriptomic datasets, and validation studies that may identify novel therapeutic targets for substance use disorder treatment.