Evaluation of antidepressant activity of ropinirole coadministered with fluoxetine in acute and chronic behavioral models of depression in rats

Abstract

Certain unknown aspects of ropinirole action, such as its antidepressant effect after chronic administration and on cotreatment with fluoxetine, remain to be evaluated, which formed the rationale for this study. Wistar rats of either sex (weighing 150-200 g) were used. In the dose-finding study, oral dose of ropinirole (20 mg/kg) was selected. This was combined with two different doses of fluoxetine (10 and 20 mg/kg). Their antidepressant-like effects were compared in acute and chronic forced-swim test (FST). Acute FST was conducted in two sessions after administration of three doses within 24 h. Chronic FST was conducted over 14 days. Drugs were administered each day for 14 days. Effect on locomotor activity was tested in OFT. ANOVA with post hoc Tukey test was used. Dose-finding study of ropinirole showed that out of three doses, 20 mg/kg produced maximum reduction in immobility in acute FST (137±8 s). Coadministration of ropinirole with fluoxetine in acute FST further reduced immobility (107±8 s). This effect was more prominent in chronic forced-swim-stressed rats (74±2 s). Neither ropinirole nor its coadministration with fluoxetine increased locomotor activity in open-field test. The potential of ropinirole to act as an antidepressant agent is proven by the reduction in immobility time in FST. Further, there is an augmentation of the effect of fluoxetine by ropinirole, suggesting synergistic interaction of dopamine and serotonin pathway in brain.