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 ۶-hydroxydopamine (۶-OHDA)-induced depression-like behavior.Methods: Parkinson was induced by the unilateral intra-nigral injection of ۶-OHDA (۸ μg/۲ μL/rat) inthe central region of the substantia nigra pars compacta (SNc). In the levodopa treatment group, ۲۱days after the injection of ۶-OHDA, the rats were treated with (i.p.) injections of levodopa (۱۵ mg/kg)for ۱۴ consecutive days. In the other group, only SPIR (۲۵ mg/kg) was added to levodopa (۱۵ 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 ۶-OHDA in the SNc increased anxiety and depression-like behavior.Our results showed that the use of levodopa (۱۵ mg/kg) treatment significantly attenuated depressionlikebehavior induced by ۶-OHDA in FST (P < ۰.۰۰۱) and TST (P < ۰.۰۰۱) in rats. Moreover, levodopa (۱۵mg/kg) + SPIR (۲۵ mg/kg) significantly reduced the symptoms of depression-like behavior induced by۶-OHDA in OFT (P < ۰.۰۵), FST (P < ۰.۰۰۱), and TST (P < ۰.۰۰۱) tests in rats.Conclusion: Based on the findings, the intra-nigral injection of ۶-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 ۶-OHDA-induced depression-like behavior in parkinsonianrats.

Keywords:

Depression , Parkinson’s disease , ۶-OHDA