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April 24, 2026
Pharmaceutical Sciences Seminar Series
(Drug ACTION Specific Seminar)
- Max Joffe, PhD
- University of Pittsburgh
Cell Type-Specific Adaptations to Prefrontal Cortex Interneurons Promote Affective Behavior in Opioid Withdrawal
Opioid use disorder (OUD) is a chronic and relapsing brain disorder that is characterized by an inability to control drug use and an intense withdrawal syndrome upon cessation. In addition to flu-like somatic symptoms, opioid withdrawal is plagued by motivational and affective disturbances that are powerful drivers of relapse. Inhibitory neurons in the prefrontal cortex (PFC) are critical regulators of adaptive behavior and express a rich endogenous opioid system. We used a combination of ex vivo whole-cell electrophysiology and in vivo fiber photometry to characterize opioid-induced adaptations to PFC IN physiology and GABAergic transmission. We show that genetically defined subtypes of interneurons undergo cell type- and receptor-specific changes to presynaptic opioid signaling following oxycodone dependence and withdrawal that bidirectionally regulate GABA release. Chronic oxycodone administration induces bidirectional changes in delta opioid receptor function at interneuron subtypes. Ongoing work employing drugs acutely restricted by tethering (DART) and CRISPR-mediated gene manipulations is revealing cell type-specific contributions to behavior.
Hosted by Cody Wenthur