Lithium potentiated, pyridoxine abolished and fluoxetine attenuated the anxiolytic effect of diazepam in mice.

In the present study, the anxiolytic effect of diazepam (1 and 2 mg/kg, i.p.) was determined alone and in combination with lithium (50 mg/kg, i.p.), pyridoxine (90 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) using elevated plus maze (EPM) and light/dark box (LDB) tests in experimental mice. The effect of various treatments on the brain GABA levels and glutamic acid decarboxylase (GAD) expression were also determined. The results obtained suggested that the diazepam (2 mg/kg, i.p.) exerted anxiolytic effect and significantly increased the brain GABA levels and GAD expression as compared to control group. Fluoxetine (10 mg/kg, i.p.) exerted anxiogenic effects, but did not affect the brain GABA levels and GAD activity significantly as compared to control. Pretreatments of pyridoxine (90 mg/kg, i.p.) abolished; lithium (50 mg/kg, i.p.) potentiated while fluoxetine (10 mg/kg, i.p.) attenuated the anxiolytic and neurochemical effects of diazepam (1 and 2 mg/kg, i.p.) treatment in mice. Therefore, the combined treatment of lithium and diazepam might be a promising treatment for anxiety.