The interactions between the
cytokine interleukin (IL)-15 and the classical
neurotransmitter GABA have been shown in IL15Rα receptor knockout mice by observations of
memory deficits and reduction of
GABA. To test the hypothesis that
IL15 affects anxiety-like behavior, knockout mice without
IL15, IL15Rα, or the co-receptor IL2Rγ were subjected to open-field and elevated plus maze tests. All three strains showed reduction of anxiety, with greater changes in the IL15Rα knockout mice than in the
IL15 or IL2Rγ knockout mice. This unexpected observation is opposite to the reported increase of anxiety in mice lacking other proinflammatory
cytokines or their receptors. The reduced anxiety was not associated with changes in associated serum
cytokines. However, Western blotting, qPCR, and immunohistochemistry all showed that IL15Rα knockout mice had mild microgliosis and
astrogliosis in the hippocampus. To determine whether this
gliosis plays a role in decreasing anxiety, IL15Rα knockout mice were treated with
minocycline, but this did not cause a change in open field performance. To determine whether
IL15 plays a direct role in anxiety, wildtype mice were treated with
IL15 by
intraperitoneal injection. This also failed to cause a change in open field behavior under the experimental conditions tested. Thus, IL15Rα is essential for normal anxiety-like behavior, but inhibition of
gliosis in the fearless IL15Rα knockout mice or
IL15 treatment of normal mice did not acutely modulate behavioral performance as tested.