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

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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