Research

The research program

The main goals of the lab are to unveil the neurobiological mechanisms underlying the transition to drug addiction and to develop novel pharmacological and non-pharmacological treatments to reduce compulsive drug seeking and taking.

Neuroscience

Neuroanatomy, cellular physiology, functional connectivity, and opto/chemogenetic dissection of the circuits of addiction.

Medication Development

Pre-IND, proof-of-concept, pharmacokinetic, and drug screening studies to move candidate treatments toward the clinic.

Behavioral Phenotyping

State-of-the-art animal models of addiction, with capacity to test over 60 animals simultaneously.

Novel Therapeutics

Deep brain stimulation and biologics as non-traditional treatments for substance use disorders.

The Addiction Biobanks

The lab maintains the Cocaine and Oxycodone Biobanks: repositories of biological specimens from more than 2,000 behaviorally and genetically characterized rats, open to the research community through the Polysubstance Addiction Research Center.

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Research projects

Neurocircuitry of drug addiction

Identifying the neural circuits mediating the effects of drugs of abuse, withdrawal, craving, and compulsive drug seeking using whole-brain 3D reconstruction with iDISCO clearing and light-sheet microscopy.

Genetic basis of cocaine and oxycodone addiction

Building tissue biobanks from over 2,000 behaviorally characterized rats — vulnerable or resistant to addiction — with brains, blood, and tissues preserved for molecular and cellular studies.

Neuronal ensembles of addiction

Identifying the discrete neuronal ensembles in the prefrontal cortex and central nucleus of the amygdala that drive compulsive alcohol and nicotine use and withdrawal.

Brain stress systems in dependence

Dissecting how corticotropin-releasing factor and dynorphin systems in the amygdala and ventral tegmental area drive escalation of alcohol, nicotine, heroin, and methamphetamine intake, using optogenetic and chemogenetic tools.

Deep brain stimulation as a treatment

Developing deep brain stimulation approaches to reduce compulsive heroin and cocaine intake.

Alcohol, nicotine, and drug inhalation models

Pioneering vapor self-administration models for alcohol, nicotine, and other drugs, with strong translational relevance to e-cigarette use.

Neuroplasticity in addiction

Investigating how drug history remodels the brain, from microtubule dynamics and neurogenesis in the hippocampus and prefrontal cortex to aging and motivational deficits.

Biomarkers of addiction and treatment response

Identifying biological markers that predict vulnerability to addiction and response to treatment, from blood signatures of opioid use to early behavioral responses that forecast later risk.

Approaches

We use a multilevel integrated approach — from genes and cells to circuits and behavior — to identify the biological mechanisms underlying addiction.

Behavioral: Addiction-like behaviors; alcohol, nicotine, and drug self-administration; oral, intravenous, subcutaneous, and vapor exposure; negative emotional states; analgesia and hyperalgesia.
Pharmacology: Proof-of-concept studies, PK/PD, dose–response, chronic studies.
Neurocircuitry: Neuroanatomy, functional connectomics, optogenetics, chemogenetics, deep brain stimulation.
Physiology: Ex vivo slice electrophysiology.
Genomics: GWAS, single-cell RNAseq, spatial transcriptomics.
Microbiome: 16S rRNA sequencing, QIIME 2, PICRUSt2.
Metabolic: Untargeted and targeted metabolomic studies.

Publications

Two decades of discovery

131 peer-reviewed papers since 2003 on nicotine, alcohol, cocaine, opioids, and more, arranged on an interactive timeline by the drug or model studied.

Explore the timeline