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

Depression has a high prevalence and high mortality and a tremendous negative impact on people’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.

Parkinson was induced by the unilateral intra-nigral injection of 6-OHDA (8 µg/2 µL/rat) in the central region of the substantia nigra pars compacta (SNc). In the levodopa treatment group, 21 days 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) as a concurrent therapy according to the treatment protocol. Anxiety and depression-like behavior were assessed by behavioral tests such as passive avoidance task (PAT), open field test (OFT), tail suspension test (TST), and forced swimming test (FST).

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 depression-like behavior induced by 6-OHDA in FST (P<0.001) and TST (P<0.001) in rats. Moreover, levodopa (15 mg/kg) + SPIR (25 mg/kg) significantly reduced the symptoms of depression-like behavior induced by 6-OHDA in OFT (P<0.05), FST (P<0.001), and TST (P<0.001) tests in rats.

Based on the findings, the intra-nigral injection of 6-OHDA into rats could cause anxiety and depression-like behavior in the fourth week onwards. Treatment with levodopa was able to attenuate stress and depressive symptoms. Additionally, our results revealed that SPIR could improve the effect of levodopa on depression-like behavior. Base on the results of this study, it is suggested that levodopa and SPIR could have some improving effects on 6-OHDA-induced depression-like behavior in parkinsonian rats.