Time-dependent effects of striatal interleukin-2 on open field behaviour in rats

There is evidence that immune messengers like cytokines can modulate emotional and motivated behaviours and are involved in psychiatric conditions like anxiety, and depression. Previously, we showed that cytokine gene expression (interleukin (IL)-2 mRNA) in specific brain tissues (striatum, prefrontal cortex) correlated with anxiety-like behaviour (open arm time) in an elevated plus-maze in rats. In a subsequent experiment, a single striatal IL-2 injection showed behavioural trends with the lower dose (1 ng) acting in a behavioural suppressive way, whereas the highest dosage (25 ng) led to activation and anxiolytic-like behaviour. Here, to support and extend our previous findings, we tested Wistar outbred rats after a single unilateral (balanced brain sites) IL-2 injection into the ventral/dorsal striatum followed by an open field test acutely and 24 h later. Analyses for horizontal locomotion showed no differences between groups. However, rats with IL-2-treatment (0.1 ng) showed a dose-dependent avoidance effect (i.e. reduced centre time) compared to the 1 ng group and vehicle controls 24 h later. In addition, suppression of free rearing activity was shown for both IL-2 doses (0.1; 1 ng) compared to saline in the acute test, and partly 24 h later. Thus, in experiment 2, we tested for proactive drug mechanisms to test for delayed effects of IL-2 as observed in experiment 1. In a new sample, rats were returned to their home cages after a striatal IL-2 injection (0.1; 0.01; 0 ng), and tested 24 h and 48 h after the injection in an open field. Neither for the first (24 h) nor for the second exposure (48 h later) did the analyses show any significant behavioural effects. We therefore suggest that emotional-related behaviour can be modulated by striatal IL-2 for at least 24 h. However, such IL-2 effects can only be observed if a mild stressful environmental challenge (i.e., forced open field exposure) is followed immediately after injection. In conclusion, proactive drug effects may be excluded for striatal IL-2 effects on open field behaviour.