Effects of drugs acting as histamine releasers or histamine receptor blockers on an experimental anxiety model in mice

Experimental anxiety in mice was evaluated using a light/dark test at 60 mi n after injection of various histaminergics. Thioperamide, a histamine H-3 receptor inhibitor (5-20 mg/kg, intraperitoneal [IPI), Compound 48/80, a ma st cell degranulator (0.1-10 mug/2 mul, intracerebroventricularly [ICV]), m epyramine, a histamine H-1 receptor antagonist (0.1-10 mug/2 mul, ICV) or c imetidine, a histamine Hz receptor antagonist (0.1 - 10 mug/2 mul, ICV) alo ne did not affect the locomotive activity, the time spent in the light zone , and number of shuttle crossings in the light/clark test. However, the tim e spent in the light zone and the number of shuttle crossings significantly decreased only when cimetidine (0.1-10 mug/2 mul, ICV) was co-treated with either thioperamide (10 mg/10 ml/kg, IF) or Compound 48/80 (1.0 mug/2 mul, ICV). The decrease in these behavioral parameters suggests induced experim ental anxiety in mice. The experimental anxiety was antagonized by mepyrami ne (10 mug/2 CL1, ICV). These results suggest that not only neuronal histam ine release induced by thioperamide but also nonneuronal (mast cells) hista mine release induced by Compound 48/80 play an important role in inducing e xperimental anxiety via postsynaptic H1 and H-2 receptors. In addition, it is likely that the anxiety may be mediated by the stimulation of H-1 recept ors, while H-2 receptors may inhibit the anxiety produced by the activation of H-1 receptors. (C) 2000 Elsevier Science Inc. All rights reserved.