Study of the Effect of Concurrent Therapy of Spironolactone With Levodopa on Depression Disorder in Male Rats

Background: Depression has a high prevalence and high mortality and a tremendous negative impact onpeople’s quality of life. This study was considered to examine the effect of levodopa and spironolactone(SPIR) in 6-hydroxydopamine (6-OHDA)-induced depression-like behavior.Methods: Parkinson was induced by the unilateral intra-nigral injection of 6-OHDA (8 μg/2 μL/rat) inthe central region of the substantia nigra pars compacta (SNc). In the levodopa treatment group, 21days after the injection of 6-OHDA, the rats were treated with (i.p.) injections of levodopa (15 mg/kg)for 14 consecutive days. In the other group, only SPIR (25 mg/kg) was added to levodopa (15 mg/kg) asa concurrent therapy according to the treatment protocol. Anxiety and depression-like behavior wereassessed by behavioral tests such as passive avoidance task (PAT), open field test (OFT), tail suspensiontest (TST), and forced swimming test (FST).Results: Intra-nigral injection of 6-OHDA in the SNc increased anxiety and depression-like behavior.Our results showed that the use of levodopa (15 mg/kg) treatment significantly attenuated depressionlikebehavior induced by 6-OHDA in FST (P < 0.001) and TST (P < 0.001) in rats. Moreover, levodopa (15mg/kg) + SPIR (25 mg/kg) significantly reduced the symptoms of depression-like behavior induced by6-OHDA in OFT (P < 0.05), FST (P < 0.001), and TST (P < 0.001) tests in rats.Conclusion: Based on the findings, the intra-nigral injection of 6-OHDA into rats could cause anxietyand depression-like behavior in the fourth week onwards. Treatment with levodopa was able to attenuatestress and depressive symptoms. Additionally, our results revealed that SPIR could improve the effect oflevodopa on depression-like behavior. Base on the results of this study, it is suggested that levodopa andSPIR could have some improving effects on 6-OHDA-induced depression-like behavior in parkinsonianrats.

Study of the Effect of Concurrent Therapy of Spironolactone With Levodopa on Depression Disorder in Male Rats Keywords:

Depression , Parkinson’s disease , 6-OHDA