Research in our laboratory is currently supported by four R01 grants. In addition, graduate students are supported by NIDA and NIH Institutional Training Grants as well as individual NRSA grants. Each of these projects and training opportunities is summarized below.
Neural Bases of Drug Context-induced Cocaine Seeking (R01DA017673)
Environmental stimuli acquire control over the addict’s behavior through associative learning processes. Research in our laboratory focuses on mapping neural circuitries and identifying neuropharmacological mechanisms through which drug-associated cues elicit relapse to drug seeking. Thus far, our findings suggest that drug-associated contexts that predict drug availability elicit drug seeking though the activation of a corticolimbic brain circuitry that includes the dorsal and ventral hippocampus, basolateral amygdala, dorsomedial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens. Dopamine D1 as well as ionotropic and metabotropic glutamate receptor stimulation in the dorsal hippocampus is necessary for drug context-induced cocaine-seeking behavior and communication between D1 and ionotropic glutamate receptors may occur through the activation of Src kinases. Functional disconnection, retroactive tracing, immunohistochemistry, Western immunoblotting, and optogenetic experiments will be conducted in order to further delineate the exact neural circuitry formed by the above brain regions. We are also interested in whether drug-induced or experience-based epigenetic changes in the relapse circuitry contribute to enhanced cue reactivity.
Drug Context-induced Cocaine Seeking: Influence of Memory Reconsolidation (R01DA025646)
Upon re-exposure to a cocaine-associated context, context-cocaine associative memories become labile and must be re-stabilized, or reconsolidated, into long-term memory in order to exert continued stimulus control over addictive behavior. Thus, pharmacological inhibition of memory reconsolidation may offer a unique approach for the treatment of addiction. Studies in our lab aim to explore the neural mechanisms through which context-cocaine associative memories are reconsolidated. So far, our studies indicate that context-cocaine memory reconsolidation is mediated by requisite interaction between protein synthesis/post-translational modification in the basolateral amygdala and sodium channel-dependent neural activity in the dorsal hippocampus. Future studies in our lab will be exploring the cellular mechanisms of this phenomenon using the contextual relapse model, pharmacological and optogenetic manipulations, as well as immunohistochemistry and Western immunoblotting.
Targeting System Xc- for the Treatment of Addiction (R01DA025617)
In a collaborative project with investigators at Marquette University and the University of Wisconsin, our laboratory participates in the in vivo behavioral testing of novel compounds for their putative anti-cocaine relapse properties. Specifically, experiments will assess the ability of the test compounds to impede context-induced relapse to cocaine-seeking behavior by facilitating the activity of the cystein-glutamate antiporter and thereby counteracting cocaine-induced imbalances in extracellular glutamate levels. This exciting endeavor may inform future clinical trials and the development of novel pharmacotherapeutics for cocaine dependence.
Neural Mechanisms of Heroin-induced Conditioned Immunomodulation (R01DA025667)
Our laboratory collaborates with Dr. Donald Lysle’s lab in the Department of Psychology to investigate the neural mechanisms through which heroin and heroin-associated environmental stimuli acquire and maintain the ability to suppress immune function. The project characterizes the neural substrates, circuitry, and the neurochemical and neuroimmunological mechanisms involved in this phenomenon using pharmacological and gene silencing manipulations as well as behavioral and molecular techniques. In future experiments, we will explore the involvement of the interleukin IL-1beta in heroin-conditioned immunomodulation as well as in drug context-induced heroin-seeking behavior.
Training Grant in Research on Drug Abuse (T32DA007244)
Our NIDA-funded institutional predoctoral training grant (Directors: Drs. Linda Dykstra and Gina Carelli) provides interdiscriplinary training in drug addiction research and financial support to some of our graduate students. Additional information about this opportunity is available at the training grant website.
Research Training in Neurosciences (T32NS007431)
The Curriculum in Neurobiology administers another NINDS-funded institutional predoctoral training grant (Director: Dr. William Snyder) that supports some of our graduate students. This training grant brings together faculty from 13 departments and provides broad training in neuroscience. More information about the training grant and the Curriculum in Neurobiology is available at the CIN website.
Ruth L. Kirschstein National Research Service Award (NRSA)
Graduate students in the Behavioral Neuroscience Program at UNC have been exceptionally successful in obtaining individual NRSA grant support from the NIH. Our students typically submit their application for this award during their second or third year in the program. Guidelines for eligibility and application information can be found at the US DHHS website.