Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice

Assessment of antidepressant-like effects of dextromethorphan on differential reinforcement of low-rate 72-s performance in rats

“…Similar effects were shown in a tail suspension test in mice, although changes in open-field activity were not shown (Nguyen and Matsumoto, 2015;Saavedra et al, 2020). On the other hand, dextromethorphan 32 mg/kg, alone or in combination with quinidine, did not exhibit antidepressant-like effects in a novelty-induced hypophagia test in mice (Saavedra et al, 2020). These findings suggest that dextromethorphan may exhibit antidepressant effects, but that further exploration in different preclinical models of antidepressant efficacy is warranted.…”

“…Ketamine also appears to reliably exhibit effects typical of clinically used antidepressant drugs in these procedures, including the DRL72s paradigm. In addition, ketamine also produces antidepressant-like effects in the novelty-induced hypophagia test, as exhibited by an increased latency to drink and volume of solution consumed, whereas quinidine and dextromethorphan exhibit an increased latency to drink but not an increased in volume consumed (Saavedra et al, 2020).…”

“…This is the first study to examine dextromethorphan in the DRL72s procedure, and to the authors’ knowledge, to evaluate antidepressant-like effects of dextromethorphan in rats. In mice, as noted earlier, dextromethorphan in combination with quinidine exhibited antidepressant-like effects in the forced swim and tail suspension tests (Nguyen et al ., 2014; Nguyen and Matsumoto, 2015; Saavedra et al ., 2020), which are generally regarded as necessary screening models for novel antidepressant drugs. Ketamine also appears to reliably exhibit effects typical of clinically used antidepressant drugs in these procedures, including the DRL72s paradigm.…”

“…Preclinically, 30 mg/kg of dextromethorphan alone (or 10 and 30 mg/kg dextromethorphan in combination with 30 mg/kg quinidine) increases immobility in a forced swim test in mice, although only the dextromethorphan 10 mg/ kg dose in combination with quinidine showed this effect in the absence of increased open-field activity (Nguyen et al, 2014). Similar effects were shown in a tail suspension test in mice, although changes in open-field activity were not shown (Nguyen and Matsumoto, 2015;Saavedra et al, 2020). On the other hand, dextromethorphan 32 mg/kg, alone or in combination with quinidine, did not exhibit antidepressant-like effects in a novelty-induced hypophagia test in mice (Saavedra et al, 2020).…”

Delta Opioid Receptor-Mediated Antidepressant-Like Effects of Diprenorphine in Mice

“…This study has identified diprenorphine as a potential rapid-acting antidepressant medication via a DOPr-mediated mechanism. Diprenorphine is effective following a single dose in the NIH assay which requires chronic dosing with traditional antidepressants and can therefore detect rapidly acting antidepressants (Dulawa et al, 2004;Saavedra et al, 2020), including ketamine (Louderback et al, 2013). Moreover, unlike many DOPr agonists and did not produce overt convulsions in mice, even at three-times the dose that produced antidepressant-like effects.…”