Experimental anxiety induced by histaminergics in mast cell-deficient and congenitally normal mice

To clarify the effect of mast cell-derived histamine release in the brain on anxiety, histaminergics-induced anxiety-like behaviors were examined by a light/dark test in mast cell-deficient (W/Wv) and congenitally normal (+/+) mice. In +/+ mice, when cimetidine (an H2 receptor antagonist) was coadministered with thioperamide (a neuronal histamine releaser acting via inhibition of H3 autoreceptors) or Compound 48/80 (C48/80, a selective histamine releaser from mast cells), the time spent in the light zone and the number of crossings between light and dark zones in a light/dark test decreased significantly, suggesting induction of anxiety. In W/Wv mice, however, experimental anxiety was induced by coadministration of thioperamide-cimetidine, but not C48/80-cimetidine. These results suggest that both nonneuronal mast cell-derived histamine and neuronal histamine play an important role in inducing experimental anxiety.