Abstract: Objective Investigate the involvement of hippocampal glutamate and NMDA receptor in the effect of CUMS on gastric function and enteric nervous system (ENS). Methods Unpredictability chronic mild stress (CUMS)-induced depression model was established in SD rats, intra-hippocampal microinjections of Glu and non-competitive antagonist of N-methyl-D-aspartic acid (NMDA) receptor (MK-801) were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by sucrose preference test and forced swimming test. The intra-gastric pressure were recorded and the expression of Nitric oxide synthase (NOS) positive neurons in myenteric nerve plexus in stomach were detected as well. Results CUMS rats showed depression-like behavioral changes and weaker gastric motility compared with control. Pretreated with MK-801 could reverse these CUMS effect, while microinjection of Glu, instead of CUMS, could increase the duration of immobility in forced swimming test, but has no effect on gastric motility. CUMS rats had lower expression of NOS positive neurons(73.74±16.38/LPF, P<0.05) and positive ganglions number(4.25±1.34/LPF, P<0.05) compared with control, but the number of NOS positive neurons in every ganglion was increased(6.55±2.37, P<0.05). Pretreated with MK-801 could rescue the decline of the number of positive ganglions. Conclusions CUMS could regulate the activity of NMDA receptor in hippocampus, and then change the configuration of NOS positive neurons in ENS, weaken the gastric motility. While the effects of CUMS on depression-like behavioral changes due to both Glu and NMDA receptor in hippocampus.

Key words: CUMS, hippocampus, Glu, gastric motility, NOS