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

The effectiveness of ketamine for treatment-resistant depression along with several other clinical advantages, such as rapid onset and reduced adverse effects associated with serotonin transporter inhibition, has garnered interest in other similar acting psychedelics as novel antidepressant drugs. The antitussive dextromethorphan exhibits glutamate N-methyl-d-aspartate receptor antagonism, sigma-1 receptor agonism, and serotonin reuptake inhibition, which has exhibited antidepressant effects in limited human studies and animal models. The present study sought to further examine dextromethorphan using a differential reinforcement of low-rate 72-s schedule, which can be used to screen antidepressant drugs, in male and female rats.