Role of paroxetine in interferon-α-induced immune and behavioural changes in male Wistar rats

Abstract

Treatment with pro-inflammatory cytokine, IFNα was documented to result in neuropsychiatric complications including depression and treatment with antidepressant, paroxetine could improve the depressive symptoms. Therefore, the effects of IFNα on behaviour and cytokine changes in the whole blood culture and in the prefrontal cortex, hypothalamus and hippocampus areas of the brain in wistar rats were investigated with emphasis on the role of paroxetine in the prevention of depressive behaviour induced by pro-inflammatory cytokines. The group of rats treated with IFNα (S.C. 50 000 IU/kg for 3 days/week for 5 weeks) was compared with three other groups; 1) saline control group (S.C. normal saline 0.2 ml/kg/day for 7 weeks), 2) paroxetine control group (paroxetine suspension orally 10 mg/kg/day for 7 weeks) and 3) group treated with paroxetine for 2 weeks followed by IFNα for 5 weeks. In open filed, the IFNα treated rats showed anxiety behaviour compared to the rats from the other groups. There was no significant difference in home cage emergence test, Morris water maze and object recognition test. There is no significant difference in plasma corticosterone between groups. The pro-inflammatory cytokines (TNFα, IL1β and IFNγ), were significantly higher whereas the anti-inflammatory cytokine, IL10 was lower in the stimulated whole blood culture of IFNα treated rats. In the brain, both pro-inflammatory cytokine IL1β and anti-inflammatory cytokine IL10 were higher in hypothalamus of the IFNα treated rats; by contrast the concentration of IL10 was lowest in hippocampus region of this group compared to the other groups. The paroxetine pretreated rats did not show these cytokine changes following IFNα treatment. Thus it appears that paroxetine pretreatment prevents the pro-inflammatory changes in blood and brain following IFNα treatment in turn prevents the anxiety behaviour.