Mouse light/dark box test reveals anxiogenic-like effects by activation of histamine H₁ receptors

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• 作者：Malmberg-Aiello ; Petra ; Ipponi ; Alessandra ; Bartolini ; Alessandro ; Schunack ; Walter
• 关键词：Anxiety ; Light/dark box test ; Histamine H₁-receptors ; Histamine H₁-receptor agonist ; Histamine H₁-receptor antagonist ; Metoprine ; Thioperamide ; 2-(3-Trifluoromethylphenyl)histamine ; Pyrilamine ; Impromidine
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2002
• 出版时间：January - February, 2002
• 年：2002
• 卷：71
• 期：1-2
• 页码：313-318
• 全文大小：130 K

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.