The anxiolytic effect of salicylic acid is mediated via the GABAergic system in the fear potentiated plus maze behavior in rats

Background Salicylic acid (SA) is a natural phenolic compound in plants with many beneficial effects for humans. The anxiolytic effect of this compound has been reported in animal models, but its mechanism of action remains unclear. In this study, by using the fear potentiated plus maze test, we evaluated the effect of salicylic acid on the gene expression of the main form of GABA (gamma aminobutyric acid) synthesizing enzyme i.e., the enzyme glutamic acid decarboxylase 67 (GAD67) which is called GAD1, in the ventral subiculum of the hippocampus, one of the main brain structures, in anxiety circuits. Also, the hypnotic effect of Salicylic acid was evaluated. Methods Animals were divided into the solvent, (SA) and diazepam treated groups (n = 6). For evaluating the anxiolytic effect of Salicylic acid, animals were subjected to 2 h of isolation, before placing them in the elevated plus maze (EPM). Afterward, the ventral part of the hippocampus was removed for evaluating the change in GAD1 gene expression by the reverse transcription-quantitative polymerase chain reaction (RTqPCR) technique. The hypnotic effect of Salicylic acid was evaluated in the ketamine induced sleeping test. Results Salicylic acid at 10 and 30 (mg/kg) increased time spent and entries to the open arms in the (EPM) (p < 0.05). (RTqPCR) revealed that 30 mg/kg of Salicylic acid increased GAD1 gene expression (p < 0.001). Salicylic acid (30 and 300 mg/kg) also increased the duration of sleep, in ketamine induced sleeping test (p < 0.05). Conclusion Our results showed that Salicylic acid has anxiolytic and hypnotic effects and it exerts its anxiolytic effect partly, via up the regulation of GAD1 in the ventral part of the hippocampus.

Automated summary

The study found that Salicylic acid has anxiolytic and hypnotic effects in animal models, partially exerting its anxiolytic effect through up-regulating GAD1 gene expression in the ventral part of the hippocampus.