Date of Award
Master of Science
Psychological Science (MS)
The noncompetitive NMDA receptor antagonist dextromethorphan and its metabolite dextrorphan have widespread effects on the central nervous system. Dextromethorphan alone and with quinidine (a CYP-450 2D6 inhibitor) have been shown to produce antidepressant effects in preclinical and clinical trials. Sex differences and the effect of estrous cycle on differential-reinforcement-of-low-rate 72 second (DRL72) responding have yet to be examined. The aim of the present study was to extend the preclinical antidepressant evidence of dextromethorphan and evaluate sex and estrous cycle influence using the DRL72 operant task in rats. Dextromethorphan (60.0 mg/kg) alone produced a decrease in responses and an increase in reinforcers. Dextromethorphan (60.0 mg/kg) with quinidine (30.0 mg/kg) produced a decrease in responses, an increase in reinforcers, and a rightward shift in the IRT peak analysis. No sex differences were found in training or testing. Furthermore, estrous cycle did not have an effect on training. These results indicate that dextromethorphan shows antidepressant effects, adding to previous literature for its potential to be used as an antidepressant in humans.
Lynch, Cayla, "Effects of NMDA Receptor Antagonists on the Differential-Reinforcement-of-Low-Rate 72 Second (DRL 72) Responding in Rats" (2020). All NMU Master's Theses. 630.
Justification for Restricting Access
I was advised by my chairperson, Dr. Adam Prus to choose an embargo period for this work. We plan to publish data from this thesis during that period.
Available for download on Wednesday, April 16, 2025