Possible Involvement of N-methyl-D-aspartate Receptor (NMDA-R) in the Antidepressant-like Effect of Trigonelline in Male Mice

Background and Aim: Depression is a mood disorder with high global prevalence. Depression is associated with a reduction in the hippocampal volume and change in its neurotransmitters function. Trigonelline is an alkaloid with neuroprotective activity. The aim of this study was to investigate the possible role of N-methyl-Daspartate (NMDA) receptor in the antidepressant-like effect of trigonelline, considering histopathological modifications of the hippocampus. Methods: 60 Naval Medical Research Institute (NMRI) male mice were divided into 6 groups including group 1 (normal saline), groups 2, 3 and 4 (trigonelline at doses of 10, 50 and 100 mg/kg), group 5 (effective dose of trigonelline plus NMDA agonist) and group 6 (sub-effective dose of trigonelline plus NMDA antagonist). Forced swimming test (FST) was used to assess depressive-like behavior. Hippocampi were separated under deep anesthesia and used for histopathological evaluation as well as NMDA receptor gene expression assessment. Results: Trigonelline at doses of 10, 50 and 100 significantly reduced the immobility time in the FST in comparison to the control group. The administration of the sub-effective dose of trigonelline plus ketamine (an NMDA receptor antagonist) potentiated the effect of the sub-effective dose of trigonelline. In addition, co-treatment of an effective dose of trigonelline with NMDA mitigated the antidepressant-like effect of trigonelline. Trigonelline at doses of 50 and 100 mg/kg significantly increased the diameter of the CA1 area of the hippocampus. Conclusion: Trigonelline showed an antidepressant-like effect in mice, probably via attenuation of NMDA receptor activity and an increase in the CA1 region of the hippocampus.