Seminar – 22nd Annual Mariann Blum Memorial Lectureship in the Neurosciences presents: Jacqueline F. McGinty, PhD

The goal of research in the McGinty Lab is to understand the neurobiology of, and develop therapeutic targets for, substance use disorders (SUDs) using rodent models. My current research is driven by two main questions. 1. What mechanisms underlie cocaine- and heroin-induced disturbances in the prefrontal cortex during abstinence that lead to drug-seeking? This work focuses on corticostriatal structural and synaptic plasticity, gene and protein activity markers, in the nucleus and dendritic spines of neurons. 2. During the last ten years, my research has demonstrated that brain-derived neurotrophic factor (BDNF) in the prefrontal cortex modulates drug-seeking in preclinical models of SUDs. A key question we have addressed is: How and via what pathways does BDNF suppress drug-seeking when it is infused into the prefrontal cortex during early withdrawal from cocaine? This research utilizes (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to manipulate defined prelimbic prefrontal projection pathways that mediate relapse to drug seeking and are regulated by BDNF.

We are members of MUSC’s NIH-funded Charleston Opioid Center on Addiction (COCA) in which we explore how the use of heroin and cocaine establishes enduring changes in plasticity-related proteins expressed in the neurons that project from the prelimbic prefrontal cortex to the nucleus accumbens core and how these drug-induced adaptations lead to cue-induced relapse. To study these neuroadaptations, we use viral-mediated expression of transgenes selectively expressed in PL-NA neurons and measure enduring and cue-induced changes in plasticity-related proteins, dendritic spine and astrocytic morphology, and synaptic glutamate-mediated currents using transgenic rats.

Our research is also supported by an individual R01 and training grant awards from NIH.