文摘
Effects of substances that are able to alter the histamine level, a histamine H1-receptor agonist and antagonist, and a histamine H2-receptor agonist were investigated in an anxiety-like state in mice by means of the light/dark box test. Diazepam was used as positive control. The histamine H3-receptor antagonist, thioperamide (2, 5, and 20 mg/kg sc), showed an anxiogenic-like effect that reached a maximum with the dosage of 5 mg/kg. The histamine-N-methyltransferase (HMT) inhibitor, metoprine (5 and 20 mg/kg sc), also decreased the time in the light at the highest dose used and, likewise, the highly selective histamine H1-receptor agonist, 2-(3-trifluoromethylphenyl)histamine (FMPH) (2.65 and 6.5 μg/mouse, icv). On the contrary, the histamine H2-receptor agonist, impromidine (3, 10, 20, and 30 μg/mouse, icv), dose-dependently showed an anxiolytic-like effect. The selective histamine H1 antagonist, pyrilamine (20 mg/kg ip) was able to prevent the anxiogenic-like effect of FMPH significantly, and that of thioperamide partially, while the effect caused by metoprine remained unvaried. It is suggested that the histaminergic system modulates anxiety-like states via the activation of both postsynaptic receptors in a contrasting manner: activation of the H1 receptor causes an anxiogenic-like effect, while that of the H2 receptors reduces anxiousness. However, on the basis of effects observed with the substances capable of releasing endogenous histamine, it seems likely that the anxiogenic-like effect is prevalent.