Effects of centrally administered H2 antagonists in the behavioral despair test

Injection of the histamine-2 (H2) receptor antagonist cimetidine into the lateral ventricles of mice produced a dose-related reduction in swimming in the behavioral despair test. This response can be attenuated by intracerebroventricular (ICV) injection of the histamine-1 (H1) receptor antagonist chlorpheniramine, or the H2 receptor agonist impromidine, given simultaneously with cimetidine. At doses which blocked cimetidine, neither chlorpheniramine nor impromidine alone had effects on swimming. A similar decrease in swimming behavior was also seen after ICV injections of the non-imidazole H2 antagonist, BMY 25,368. This effect of BMY 25,368 was also attenuated by chlorpheniramine and impromidine. These results suggest that H1 and H2 receptors in the brain may mediate opposing behavioral effects.