Alteration of Depressive-like Behaviors by Psilocybe cubensis Alkaloid Extract in Mice: the Role of Glutamate Pathway

Psilocybin, the active compound in Psilocybe cubensis extract (PCE), shows antidepressant and anxiety-related effects in mice by potentially interacting with the NMDA glutamate receptor. In experiments, a high dose of PCE (100 mg/kg) altered locomotion and time spent in the center of an open field. Lower doses of PCE (10 or 40 mg/kg) or ketamine (1 mg/kg) alone did not change locomotor activity, but combining these subeffective amounts reduced immobility in forced swimming and tail suspension tests, indicating antidepressant-like effects. These results suggest that psilocybin's interaction with the NMDA receptor may contribute to its antidepressant properties.

Study at a glance

Abstract

Background and objectives: Considering the increasing prevalence of depression, many studies are launched to investigate new antidepressant treatments. The present research has shown how psilocybin as an active compound of Psilocybe cubensis (Earle) Singer extract (PCE) can change the parameters related to depression and anxiety in animal models. Both serotonin (5-hydroxytryptamine: 5-HT) and glutamate modulate depressive-like behaviors and, therefore, we examined the possible interaction of psilocybin as 5-HT1 agonist with glutamate receptor N-methyl-D-aspartate (NMDA). Methods: Psilocybe cubensis extract of this mushroom was prepared by ethyl acetate. NMRI mice involved in all experiments and were treated with the vehicle, extract, or standard drug intraperitoneally. Open field (OFT), forced swimming (FST) and tail suspension tests (TST) were applied to measure the intended parameters. OFT was performed to verify the applied doses for measuring the following antidepressant activity. Results: PCE at the doses of 100 mg/kg significantly changed the locomotion, time spent in center and velocity of the animals in OFT. While treatment of the animals with PCE 10 and 40 mg/kg or ketamine 1 mg/kg did not alter the locomotor activity, co-administration of these subeffective amounts significantly reduced the immobility time in both FST and TST. Conclusion: These effects may indicate possible implication of psilocybin with NMDA receptor which consequently produces the antidepressant effects.