Yu-Cheng Ho
Mackay Medical College, Taiwan
Title: Ketamine metabolite rescues chronic stress-induced depression in rats
Biography
Biography: Yu-Cheng Ho
Abstract
Statement of the Problem: Major depressive disorder affecting more than 100 million people worldwide every year is a heterogeneous illness. To date, current pharmacotherapies require prolonged administration from several weeks to months for an appreciable response. This is particularly concerning given that suicide risk is elevated in subjects with depression.
Methodology & Theoretical Orientation: It is still unclear that whether ketamine metabolite (2R,6R-hydroxynorketamine; 2R,6R-HNK) rescues chronic stress-elicited depression-like behavior. Depression-like behavior in the rats were induced by learned helplessness (LH) procedure. Forced swim test (FST) and sucrose preference test (SPT) were used to study the depression-like behavior. Findings: Rats receiving learned helplessness procedure exhibited high failure rate in the escapable footshock test compared to control group. LH rats exhibited an increase in immobile time during the FST and a reduction in sucrose consumption. Intraperitoneal ketamine metabolite, 2R,6R-HNK, injection decreased immobile time during the FST and increased sucrose consumption in LH rats.
Conclusion & Significance: Ketamine metabolite 2R,6R-HNK rescues LH-induced depression-like behavior including despair behavior and anhedonia. These results may pave the foundation for a critical issue that ketamine metabolite, 2R,6R-HNK plays crucial roles in stress-induced depression-like behaviors and provides a new insight into depression management and development of antidepressants.