Background & aim: It has been suggested that histamine has modulatory influence on anxiety-related behaviors both in animals and humans. On the other hand, GABA (A) receptor modulating drugs such as benzodiazepines have been used to treat anxiety disorders. Co-administration of the aforementioned drugs would be of high interest in terms of anxiety effects.

Method & Materials: In the present study, we investigated the anxiety-related effects of individual and combined intraperitoneally administration of histamine and diazepam, a benzodiazepine agent. To do so, anxiolytic indices of Open Arm Times (%OAT) and Open Arm Entries (%OAE) were measured using an elevated plus-maze test of anxiety on rats.

Results: Intraperitoneal histamine administration 20 (mg/kg) decreased %OAT, but not locomotor activity, showing an anxiogenic response. Subcutaneous administration of diazepame at dose of 1 mg/kg increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. Subcutaneous administration of diazepame, at doses of 1 mg/kg before histamine (20 mg/kg) increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response.

Conclusion: Our results indicated that the anxiogenic effects induced by histamine in the intraperitoneal could be reversed in the presence of diazepam.