Center for Study of Opioid Receptors and Drugs of Abuse (CSORDA)
The research objectives of CSORDA are to gain insights into the mechanisms of action of endogenous opioids and opioid drugs at their cognate receptors with the goal of discerning fundamental processes contributing to behaviors such as analgesia, addiction, tolerance and withdrawal. The current focus is on the circuitry and cell-specific adaptations underlying addiction-related behaviors mediated by mu opioid receptors. The center will focus on the circuitry of reward processing with the renewal emphasizing study of the circuitry regulating dysphoric states and relapse following abstinence of opiate drugs including in different susceptibility models including neuropathic pain and PTSD.
CSORDA funds four Research Projects that are highly interactive both thematically and technically use shared models, reagents and methodologies. Projects will focus on different brain circuitry associated with reward/aversion and employ mouse genetics and behavioral analysis combined with electrophysiology, optogenetics, transcript analysis and brain imaging. The four projects are:
- Project I: Genetic Dissection of Striatal Indirect-Pathway in Opioid Withdrawal Aversion (Leads - Nigel Maidment and William Yang). This Project focuses on the D2-MSN cell type of the indirect pathway from the nucleus accumbens to the ventral pallidum,that both published and preliminary data indicate is critical in mediating both the aversive effects of opioid withdrawal and basal MOR-hedonic tone.
- Project II: Mu Opioid receptors in Habenular Networks: Reward and/or Aversion? (Lead - Brigitte Kieffer). Project II is focused on habenula circuitry.
- Project III: Impact of Chronic Pain on Circuitry Involved in Opioid Self-Administration Behaviors (Lead - Chris Evans; Co-investigator Catherine Cahill). This Project uses iv self-administration of the opioids, remifentanil, oxycodone and morphine, combined with genetic manipulations, to determine phases in self administration influenced by MOR in different neural populations, and how this impacts self-administration in chronic pain.
- Project IV: Bidirectional Comorbidity Between Fear Sensitization and Opioid Reward (Lead - Michael Fanselow). Component IV will use a rodent stress-induced PTSD model (Stress-Enhanced Fear Learning - SEFL) developed in Dr Fanselow’s laboratory to begin to explore the circuitry that may underlie the co-morbidity of PTSD and opioid abuse, and other drugs of abuse.
The Administrative Core and CSORDA Advisory board, consisting of Drs Balleine, Chavkin, Bonci, Levitt, Nestler and Whybrow ex-officio, will provide programmatic oversight and coordinate training, outreach and a vigorous Pilot Program for the center. (Lead: Chris Evans) (CoI’s Nigel Maidment and Eydie London)
The Technical Advancement Core will maintain CSORDA as a technically cutting edge and innovative center which will enable CSORDA’s research plan to incorporate the very latest technologies in animal resting-state MRI, multilectrode array recording, transcript profiling, optogenetics and cellular calcium imaging with methodologies specifically optimized for CSORDA research. ((Leads: William Yang and Peyman Golshani) (Co-I’s Giovanni Coppola, Sotiris Mansmanidis and Brigitte Kieffer)
The Animal Breeding Core will supply all CSORDA Projects with mouse models and extend facilities into the research community (Leads: William Yang)
The Pilot Core will fund 4 Pilot Program grantees, each year to enhance the contribution of CSORDA to addiction research.