Pretreatment with l-histidine produces a shift from methamphetamine-induced stereotypical biting to persistent locomotion in mice

The administration of methamphetamine (METH; 10 mg/kg, i.p.) to male ICR mice induced bizarre behaviors including persistent locomotion and stereotypical behaviors, which were classified into four categories: stereotypical head-bobbing, circling, sniffing, and biting. Pretreatment with l-histidine (750 mg/kg, i.p.) significantly decreased the stereotypical biting induced by METH and significantly increased persistent locomotion. This effect of l-histidine on behavior was completely abolished by simultaneous administration of pyrilamine or ketotifen (brain-penetrating histamine H₁ receptor antagonists; 10 mg/kg each, i.p.), but not by the administration of fexofenadine (a non-sedating histamine H₁ receptor antagonist that does not cross the blood-brain barrier; 20 mg/kg), zolantidine (a brain-penetrating histamine H₂ receptor antagonist; 10 mg/kg), thioperamide, or clobenpropit (brain-penetrating histamine H₃ receptor antagonists; 10 mg/kg each). The histamine content of the hypothalamus was significantly increased by l-histidine treatment. These data suggest that l-histidine modifies the effects of METH through central histamine H₁ receptors.