To explore the effect of fingolimod (FTY720) on depressive behavior in depressive disorder rats and its related mechanism.

The SD rats were divided into the following groups: Control group (normal feeding), model group (depression model construction), and low, medium, high groups (administering 0.1, 0.3 and 1.0 mg·kg^-1 FTY720 prior to constructing the depression model, respectively), with 10 rats in each group. The hippocampal tissue morphology was assessed using hematoxylin-eosin (HE) staining; depression symptoms were evaluated through the sucrose preference test; cognitive function was assessed using the Morris water maze test; neuronal apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL); levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway-related proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence; dopamine (DA) content in different brain regions was analyzed by high-performance liquid chromatography.

After different treatments, the sugar-water preference rates in control, model and low, medium, high groups were (81.95±9.06)%, (59.72±8.32)%, (62.34±7.58)%, (68.08±7.94)% and (79.61±9.25)%, respectively; the escape latencies were (18.73±2.06), (34.25±3.87), (31.64±2.92), (25.97±2.43) and (19.86±1.95) s, respectively; apoptosis rates were (3.93±0.65)%, (28.75±5.94)%, (24.63±3.21)%, (15.27±2.58)% and (6.08±1.74)%, respectively; NLRP3 mRNA relative expression levels were 1.00±0.17, 4.89±0.64, 4.31±0.72, 2.52±0.58 and 1.87±0.25; ASC mRNA relative expression levels were 1.00±0.14, 2.67±0.53, 2.28±0.39, 1.54±0.26 and 1.39±0.21; DA contents in PFC region were (795.42±64.38), (547.93±52.65), (571.08±51.97), (662.45±73.89) and (748.96±81.53) μg·g^-1; DA contents in NAc region were (2 186.53±124.97), (1 672.84±109.25), (1 769.65±112.14), (1 904.27±106.63) and (2 065.92±127.58) μg·g^-1; DA contents in the VTA region were (1 765.83±108.29), (1 316.73±115.84), (1 378.52±94.36), (1 494.76±103.21) and (1 653.94±108.45) μg·g^-1. Compared with the control group, the above indexes in the model group were statistically significant (all P<0.001). Compared with the model group, the above indexes in the middle dose group were statistically significant (all P<0.05). Compared with the model group, the above indexes in the high dose group were statistically significant (all P<0.001).

FTY720 can regulate neuronal damage and cognitive function in depressed model rats, and its antidepressant mechanism may be related to inhibiting the activation of NLRP3 inflammasome pathway and increasing the content of DA in the neural circuit of PFC-ARC-VTA.