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

University of Maastricht, MD Maastricht, The Netherlands, a.mu{at}np.unimaas.nl, Clinical Biochemistry, University of Antwerpen, Antwerpen, Belgium

S. O'Mahony

University of Maastricht, MD Maastricht, The Netherlands

M. Kubera

Department of Experimental Endocrinology, Polish Academy of Science, Krakow, Poland

Y.K. Kim

Korea University Medical Centre, Korea University, Seoul, Korea

C. Kenny

University of Maastricht, MD Maastricht, The Netherlands

A. Kaim-Basta

Department of Experimental Endocrinology, Polish Academy of Science, Krakow, Poland

H.W.M. Steinbusch

University of Maastricht, MD Maastricht, The Netherlands

B.E. Leonard

University of Maastricht, MD Maastricht, The Netherlands

Treatment with pro-inflammatory cytokine, IFN was documented to result in neuropsychiatric complications including depression and treatment with antidepressant, paroxetine could improve the depressive symptoms. Therefore, the effects of IFN 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 IFN (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 IFN for 5 weeks. In open filed, the IFN 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 (TNF, IL1ß and IFN), were significantly higher whereas the anti-inflammatory cytokine, IL10 was lower in the stimulated whole blood culture of IFN treated rats. In the brain, both pro-inflammatory cytokine IL1ß and anti-inflammatory cytokine IL10 were higher in hypothalamus of the IFN 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 IFN treatment. Thus it appears that paroxetine pretreatment prevents the pro-inflammatory changes in blood and brain following IFN treatment in turn prevents the anxiety behaviour.

Key Words: interferon- • proinflammatory cytokine • IL-10 • anxiety • depression

Journal of Psychopharmacology, Vol. 21, No. 8, 843-850 (2007)
DOI: 10.1177/0269881107077165


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