Preclinical evidence of a rapid-onset antidepressant-like effect of Pseudospondias microcarpa hydroethanolic leaf extract in a chronic depression model

Abstract

Background: Depression is a widespread, devastating mental illness and currently available treatments have significant limitations including low response rates and delayed onset of action. N-methyl-D-aspartate (NMDA) receptor antagonists exert fast-acting antidepressant effects. Pseudospondias microcarpa produces an antidepressant-like effect via inhibition of the glycine/NMDA receptor complex, and could therefore possess a rapid onset of action. Therefore, the present study investigated the possible rapid-onset antidepressant action of P. microcarpa in mice. Methods: In this study, rapid-onset and sustained antidepressant effects of the hydroethanolic leaf extract of P. microcarpa (PME) was investigated in the open-space swim test, a chronic model of depression. Antidepressant effect was further assessed in the tail suspension test (TST). In addition, the effect of the extract on cognitive function in the Morris water maze (MWM) test was investigated. Results: Depressed mice showed a significant increase in immobility and decrease in distance swum. However, treatment with PME and the classical antidepressants significantly decreased immobility time and increased distance swum. Furthermore, unlike the classical antidepressants which required 10-14 days to significantly improve mobility behaviour, PME treatment significantly decreased immobility time (P<0.001) on the first day of treatment (day 5 of stress procedure). This effect was also sustained for the remainder of the experiment. The extract also significantly decreased immobility time in the TST (F3,16=4.881, P=0.0135) and decreased escape latency (F4,24=12.07, P<0.0001) in the MWM procedure. Conclusions: The leaves of P. microcarpa exhibits rapid and sustained antidepressant effects and improve cognitive function in depressed mice.