Projects Overview

Project 1
Drug-induced ROS and epigenetic mechanisms
(PI: Dr. Christopher Cowan)
The primary goal of this project is to test two hypotheses: 1) cocaine- or heroin-induced oxidative stress modifies HDAC5 cysteine thiol groups in the nucleus accumbens, which limits the epigenetic anti-drug seeking actions of HDAC5, and 2) the anti-drug seeking effects of repeated N-acetylcysteine (NAC) treatment are due, at least in part, to its ability to protect HDAC5 from ROS signaling events that promote nuclear exclusion.

Project 2
Preventing drug-induced neuroadaptations in prelimbic cortical signaling
(PI: Dr. Jacqueline McGinty)
In Project 2, we have found that heroin abstinence: 1) triggers dysregulation of intrinsic excitability and synaptic plasticity of Drd1 and Drd2 prelimbic (PL) cortical neurons projecting to nucleus accumbens, 2) causes hyperactivity of cAMP-dependent PKA in PL cortex, and (3) and that these neuroadaptations can be prevented by local injections of a PKA inhibitor that decreases relapse to heroin seeking.

Project 3
Tetrapartite synapses regulate cue-induced drug seeking
(PI: Dr. Peter Kalivas) 
Project 3 has three goals. 1) Characterize heroin and cocaine cue-induced changes in accumbens astroglia morphology and determine the role of astroglial plasticity in drug seeking. 2) Determine which cell types undergo enduring and transient adaptations in tetrapartite synaptic physiology and morphology. 3) Recapitulate in rodents the cTBS and NAC treatments used in Project 4 to reverse cued drug seeking and cocaine- and heroin-induced tetrapartite neuroadaptations.

Project 4
Neurocircuit strategy to decrease cocaine cue reactivity
(PI: Dr. Bashar Badran   Co-Is: Drs. Kelly Barth, Jeff Borckardt, and Xiaolong Peng) 
The overarching goal of this clinical project is to determine the efficacy of continuous theta burst stimulation (cTBS) and NAC as tools to restore cocaine impaired corticostriatal circuitry function measured using fMRI, and to dampen cocaine cue reactivity among treatment-engaged individuals.