Our laboratory is interested in the neurobiological mechanisms of drug addiction and relapse. We seek to understand the neuroscience underlying the compulsive and maladaptive behaviors associated with this devastating psychiatric disorder. To understand how brain circuits contribute to behavior, the lab uses rodent models of addiction, including the self-administration paradigm.
Habitual and compulsive cocaine seeking.
One of the most insidious aspects of drug addiction is that afflicted individuals are plagued by an uncontrollable drive to seek and use drugs, despite harmful consequences or the desire to quit. Recent novel rodent models of drug addiction have been developed specifically to better understand the mechanisms underlying the loss of control that occurs with the addiction process, and have found that a subset of rats will compulsively seek cocaine despite the delivery of aversive consequences. These models generally focus on drug-seeking behavior that has become either habitual (automatically triggered by stimuli) or compulsive (insensitive to negative consequences). Ongoing studies in our lab are investigating possible relationships between habitual and compulsive drug seeking to better understand the development of addiction behavior.
Neurocircuitry and transmitter systems underlying cue-induced relapse.
Drug-associated cues are known to be powerful triggers of relapse in addicts and to drive reinstatement of drug seeking in animal models. Human addicts show stress- and anxiety-like reactions to drug cues, indicating that cue- and stress-induced relapse might have significant overlap in terms of neurocircuitry and psychological mechanisms. Current studies in the lab are aimed at exploring how neural systems typically associated with stress (norepinephrine, CRF, and imidazoline) are involved in cue-induced drug seeking.
Opposing behavioral roles played by PFC subpopulations.
Another project currently being pursued in the lab involves investigating subpopulations of neurons in the prefrontal cortex (PFC), a brain area that plays an important role in addiction and inhibitory control. We are investigating two subpopulations that distinctly project to either the nucleus accumbens (NAc) or rostromedial tegmental nucleus (RMTg). These two output structures are often associated with opposing behavioral outcomes, including roles for NAc in driving reinstatement and RMTg in driving inhibition of behavior. We are investigating whether these two projection pathways from PFC play opposing roles in cue-induced reinstatement.
Animal behavior: drug and food self-administration, operant conditioning
Brain/neural manipulations: optogenetics, DREADDs, virus technologies, pharmacology, lesions
Anatomical techniques: retrograde/anterograde tracing, transsynaptic tracing with
modified rabies virus, protein immunohistochemistry, mRNA in situ hybridization histochemistry