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Updated: Jun 18, 2026

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Pretreatment with l-histidine produces a shift from methamphetamine-induced stereotypical biting to persistent
Junichi Kitanaka1, Nobue Kitanaka, Tomohiro Tatsuta
1Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan. kitanaka-hyg@umin.net
Abstract:
The administration of methamphetamine (METH; 10mg/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 H(1) receptor antagonists; 10mg/kg each, i.p.), but not by the administration of fexofenadine (a non-sedating histamine H(1) receptor antagonist that does not cross the blood-brain barrier; 20mg/kg), zolantidine (a brain-penetrating histamine H(2) receptor antagonist; 10mg/kg), thioperamide, or clobenpropit (brain-penetrating histamine H(3) receptor antagonists; 10mg/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 H(1) receptors.
Insights
L-histidine administration reduced methamphetamine-induced biting in mice by affecting central histamine H(1) receptors. This dietary supplement altered behaviors, suggesting a role for histamine in stimulant-induced effects.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Methamphetamine (METH) induces complex behavioral changes, including locomotion and stereotyped actions.
- Histamine plays a role in regulating various physiological and behavioral processes in the central nervous system.
Purpose of the Study:
- To investigate the effect of L-histidine on methamphetamine-induced behaviors in mice.
- To explore the potential involvement of histamine receptors in mediating these behavioral effects.
Main Methods:
- Male ICR mice were administered methamphetamine (10mg/kg) to induce behaviors like head-bobbing, circling, sniffing, and biting.
- Mice were pretreated with L-histidine (750 mg/kg) alone or in combination with various histamine receptor antagonists.
- Behavioral changes and hypothalamic histamine levels were assessed.
Main Results:
- L-histidine significantly reduced METH-induced biting and increased locomotion.
- These effects were blocked by brain-penetrating histamine H(1) receptor antagonists (pyrilamine, ketotifen) but not by a non-sedating H(1) antagonist or H(2)/H(3) antagonists.
- Hypothalamic histamine levels increased following L-histidine treatment.
Conclusions:
- L-histidine modulates methamphetamine-induced behaviors, specifically targeting stereotypical biting.
- The findings strongly suggest that central histamine H(1) receptors are involved in mediating the behavioral effects of L-histidine in the context of METH administration.
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