Role of paroxetine in interferon-alpha-induced immune and behavioural changes in male Wistar rats.
Treatment with pro-inflammatory cytokine, IFNalpha was documented to result in neuropsychiatric complications including depression and treatment with antidepressant, paroxetine could improve the depressive symptoms. Therefore, the effects of IFNalpha 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 IFNalpha (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 IFNalpha for 5 weeks. In open filed, the IFNalpha 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 (TNFalpha, IL1beta and IFNgamma), were significantly higher whereas the anti-inflammatory cytokine, IL10 was lower in the stimulated whole blood culture of IFNalpha treated rats. In the brain, both pro-inflammatory cytokine IL1beta and anti-inflammatory cytokine IL10 were higher in hypothalamus of the IFNalpha 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 IFNalpha treatment. Thus it appears that paroxetine pretreatment prevents the pro-inflammatory changes in blood and brain following IFNalpha treatment in turn prevents the anxiety behaviour.
Myint
A M
AM
University of Maastricht, MD Maastricht, The Netherlands. a.mu@np.unimaas.nl
O'Mahony
S
S
Kubera
M
M
Kim
Y K
YK
Kenny
C
C
Kaim-Basta
A
A
Steinbusch
H W M
HW
Leonard
B E
BE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D003345:Corticosterone; D016207:Cytokines; D016898:Interferon-alpha; D007371:Interferon-gamma; D016753:Interleukin-10; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014409:Tumor Necrosis Factor-alpha