OVERALL RESEARCH INTEREST
Translational research on PTSD and substance use disorders using molecular, biochemical, in vivo brain imaging, and behavioral approaches.
EFFECTS OF POST-TRAUMA KETAMINE INFUSION ON STRESS HORMONES, FEAR MEMORY, AND BRAIN ENERGY UTILIZATION IN MALE AND FEMALE RATS
Ketamine is the most common battlefield analgesic administered to traumatically injured service members in recent wars. Endorsed by the committee for Tactical Combat Casualty Care (TCCC), ketamine presents significant advantages over traditional opioid analgesics during the combat care, namely hemodynamic stability and preservation of respiration. However, peri-trauma administration of ketamine produces dissociation and hallucination, which may contribute to the formation of dysfunctional fear memories. We found that subanesthetic IV ketamine infusion after fear conditioning dose-dependently enhanced fear memory and in vivo regional glucose utilization in fear and stress sensitive regions such as hypothalamus, amygdala, and hippocampus of rats.
Radford KD, Park TY, Jaiswal S, Pan H, Knutsen A, Zhang M, Driscoll M, Osborne-Smith LA, Dardzinski BJ, and Choi KH (2018) Enhanced fear memories and brain glucose metabolism (18F-FDG PET) following sub-anesthetic intravenous ketamine infusion in Sprague Dawley rats. Translational Psychiatry 8(1): 263 PMID: 30504810
PRECLINICAL EXAMINATION OF THE GATEWAY HYPOTHESIS OF DRUG ADDICTION
The Gateway Hypothesis of drug addiction is based on epidemiological data and states there is a progression of drug use from use of a softer drug (e.g., nicotine) to use of a harder drug (e.g., opioid). We investigated whether the Gateway Hypothesis involves a causal progression. The animals received a clinically relevant dose of nicotine or saline for 3 weeks via osmotic minipump and subsequently were allowed to self-administer IV morphine (3 h/day) for 10 days. Our results do not support the Gateway Hypothesis. In fact, rats pre-exposed to chronic nicotine self-administered significantly less morphine than did rats pre-exposed to saline. These findings may be relevant to future drug use prevention policies and programs.
Eklund KE, Nishida KS, Barry ES, Choi KH, and Grunberg NE (2019) Examination of the gateway hypothesis in a rat model. Pharmacology Biochemistry & Behavior Apr;179:89-97, PMID: 30797762