Please, join the Department of Pharmacology, Addiction Science, and Toxicology for our (PHAST) Spring 2026 seminar.
Wednesday, April 29, 2026, in CRB 114 Auditorium
12:00pm – 1:00pm
Presenter: Dr. Giordano de Guglielmo, University of California, San Diego Department of Psychiatry
Hosted by Dr. Hao Chen
Brief summary of presentation:
To bridge the translational gap in addiction research, we utilize Heterogeneous Stock (HS) rats to model human genetic diversity and capture individual variability in addiction-like behaviors. We employ a high-throughput behavioral pipeline that profiles motivation, compulsivity, and somatic withdrawal to stratify “addiction-like” phenotypes beyond simple drug intake.
Using a forward genetics approach, we identified P2rx4 as a novel target via GWAS. By applying a Genetically Regulated Expression (GReX) prediction model, we demonstrated that predicted P2rx4 expression correlates with alcohol intake in naïve animals, and pharmacologically validated this target using Ivermectin in dependent rats. Complementing this, our reverse translation efforts validated the human GWAS hit Chrna5/a3/b4, showing that the α3β4 partial agonist ATRX-52 restores GABAergic transmission in the central amygdala and reduces alcohol seeking in vulnerable populations.
Furthermore, leveraging our tissue biobank and single-nucleus RNA sequencing, we identified mitochondrial dysfunction as a key driver of dependence. We show that chronic NAD+ treatment attenuates withdrawal and relapse in both opioid and alcohol models. In contrast, we demonstrate that manipulating Crhbp reveals drug-specific mechanisms, where knockdown reduces cocaine seeking but increases oxycodone seeking. Finally, we address the complexity of polysubstance use, demonstrating distinct neuroadaptations in opioid-cocaine co-use models to advance precision medicine
Join Zoom Details
Meeting ID: 811 6120 1688
Passcode: 484834