Pre-clinical research projects

Drug-induced plasticity in the midbrain

The TN² lab investigates opioid-induced neuroadaptations in dopamine neurons that could underlie vulnerability to relapse, which persists in rodent models of addiction and in patients with substance use disorders even after prolonged abstinence. We identify such drug-induced changes using patch-clamp electrophysiology and molecular imaging techniques and then test their physiological relevance and effect on cue reactivity using multi-array single unit recordings in awake behaving rats. 

TMS effects on circuit plasticity and drug seeking in rodents

The TN² lab studies the neurobiological effects of Transcranial Magnetic Stimulation (TMS) on brain circuits distal to the site of TMS stimulation by taking advantage of the anatomy of the olfactory circuit. This project allows us to answer fundamental questions about the neurobiological effects of TMS. For example, it is not clear 1) whether TMS of the brain surface induces lasting synaptic and intrinsic changes in downstream cortical and subcortical circuits, 2) how different TMS parameters affect downstream circuits, and 3) whether TMS can reverse established circuit pathologies in animal models of drug addiction. Answering these questions will allow the development of more effective and safer clinical TMS protocols tailored to specific circuit pathologies. We recently developed and validated a non-invasive opioid self-administration mouse model using vaporized fentanyl (Moussawi et al., Science Advances 2020), which we use for TMS investigations.

Role of the olfactory tubercle in reward and motivation

The olfactory tubercle is a brain region representing an anatomical and functional extension of the ventral striatum, which plays a critical role in drug addiction in humans. However, the role of the olfactory tubercle in drug reward and vulnerability to relapse has not been investigated. Studies from the TN² lab show profound drug-induced changes in the physiology of medium spiny neurons of the olfactory tubercle in rodents.

Clinical research projects

Identifying new neuromodulation targets for drug addiction

Deep Brain Stimulation (DBS) is a technique most commonly used to treat movement disorders, such as Parkinson’s Disease. The TN² lab is interested in exploring the application of DBS of the limbic pallidum to treat severe and refractory cases of drug addiction. We have recently started a clinical trial of limbic pallidum DBS for severe and refractory alcohol use disorder. Furthermore, in a recent collaboration with Dr. Michael Fox at the Laboratory for Brain Network Imaging and Modulation at Harvard Medical School, we used lesion network mapping to identify an ‘addiction remission network’, which highlights specific targets for neuromodulation to treat drug addiction.

The effects of Globus pallidus DBS on impulsivity and motivation

In collaboration with neurologist Dr. Kelly Mills at Johns Hopkins, we examined the role of globus pallidus DBS in Parkinson’s Disease patients on impulsivity and motivation. Such studies are relevant to our lab’s primary interest in substance use disorders as impulsivity and motivational changes are core features of drug addiction.