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.
","abstract_html":"<p>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.</p>","abstract_has_math":false,"creators":["Lynch, Cayla"],"institution":null,"degree_name":"Master of Science","degree_level":"Thesis","degree_discipline":"Psychological Science","degree_department":null,"school":null,"contributors":["Adam Prus"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-04-01T07:00:00Z","date_published":"2020-04-01T07:00:00Z","updated_at":"2026-07-24T03:24:17Z","subjects":["DRL 72","antidepressant","NMDA receptor antagonist","dextromethorphan","quinidine","sex differences","estrous cycle","differential reinforcement of low rate 72 second","Other Psychology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.nmu.edu/theses/630","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Adam Prus"]},{"key":"dc:creator","label":"Author","values":["Lynch, Cayla"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2025-04-16T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Psychological Science"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["DRL 72","antidepressant","NMDA receptor antagonist","dextromethorphan","quinidine","sex differences","estrous cycle","differential reinforcement of low rate 72 second","Other Psychology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.nmu.edu/theses/630"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Effects of NMDA Receptor Antagonists on the Differential-Reinforcement-of-Low-Rate 72 Second (DRL 72) Responding in Rats"]}]}],"canonical_facts":{"dc:contributor":["Adam Prus"],"dc:creator":["Lynch, Cayla"],"dc:date.available":["2025-04-16T07:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["https://commons.nmu.edu/theses/630"],"dc:subject":["DRL 72","antidepressant","NMDA receptor antagonist","dextromethorphan","quinidine","sex differences","estrous cycle","differential reinforcement of low rate 72 second","Other Psychology"],"dc:title":["Effects of NMDA Receptor Antagonists on the Differential-Reinforcement-of-Low-Rate 72 Second (DRL 72) Responding in Rats"],"thesis:degree_discipline":["Psychological Science"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T03:24:17Z"}