It is assumed that cytokines (like interleukins) can infl uence depression and anxiety. Interleukin-2 (IL-2) is suggested to be one factor, which may mediate behavioural and neurochemical (e.g., serotonergic) features of depression in the brain. Previously, we have shown in rats that IL-2 mRNA in the striatum and prefrontal cortex is correlated with anxiety-like avoidance behaviour in an elevated plus-maze. Additionally, striatal IL-2 microinjections affected anxiety-like behaviour in a biphasic way. In the present study, we investigated the impact of systemically (i.p.) injected IL-2 (2.5 μg/kg) on serotonegic (5-HT) and dopaminergic neurotransmission in various cortical areas by in-vivo microdialysis in anaesthetised rats (Exp. 1). Furthermore, based on the serotonergic time profi le, we conducted two experiments to test for delayed (test 2 h post injection, Exp. 2) and acute (Exp. 3) behavioural effects of systemic IL-2 (0–5 μg/kg) on depression-related behaviour in a forced swim test (FST). The neurochemical results revealed that systemic IL-2 lastingly reduced extracellular 5-HT levels in the medial prefrontal (−75%), occipital (−70%), and temporal cortices (−45%). In contrast, dopamine was moderately reduced only in the medial prefrontal cortex. The functional relevance of these specifi c neurochemical changes were supported by the subsequent behavioural evaluation showing IL-2 dose-dependent effects on depression-related behaviour in the FST after delayed testing.
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