The Anxiolytic effect of salicylic acid is mediated via the GABAergic system

Abstract

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 synthesizing enzyme i.e., the enzyme glutamic acid decarboxylase 67 (GAD67), in the ventral subiculum of the hippocampus. Also, the hypnotic effect of Salicylic acid was evaluated. 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 hours 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 (GAD67) 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. Our results showed that Salicylic acid at 10, 30 (mg/kg) increased time spent and entries to the open arms in the (EPM) (p < 0.05). (RTqPCR) revealed that 30mg/kg of Salicylic acid increased (GAD67) 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). Our results showed that Salicylic acid has anxiolytic and hypnotic effects and it exerts its anxiolytic effect partly, via up regulation of (GAD67) in the ventral part of the hippocampus.