Elsevier

Neuroscience

Volume 147, Issue 3, 13 July 2007, Pages 765-777
Neuroscience

Neuropharmacology
Blockade of brain histamine metabolism alters methamphetamine-induced expression pattern of stereotypy in mice via histamine H1 receptors

https://doi.org/10.1016/j.neuroscience.2007.05.006Get rights and content

Abstract

The administration of methamphetamine (METH, 10 mg/kg, i.p.) to male ICR mice induced stereotyped behavior consisting of nail and/or wood chip biting (86.0%), continuous sniffing (12.0%), head bobbing (1.1%), and circling (1.0%) during the observation period of 1 h. Pretreatment of the mice with metoprine (2, 10, and 20 mg/kg, i.p.), a selective inhibitor of histamine N-methyltransferase (HMT), which metabolizes histamine in the brain, significantly increased and decreased METH-induced continuous sniffing (20.5, 51.3, and 80.3%) and nail and/or wood chip biting (77.4, 45.3, and 14.2%), respectively, in a dose-dependent manner. The hypothalamic contents of histamine and its metabolite Nτ-methylhistamine were significantly increased and decreased by metoprine (10 mg/kg, i.p.), respectively. The metoprine action on METH-induced behavior was completely abolished by pyrilamine (10 and 20 mg/kg) and ketotifen (10 mg/kg), selective, centrally acting histamine H1 receptor antagonists, but not by fexofenadine (20 mg/kg), zolantidine (10 mg/kg) and thioperamide (10 mg/kg), a peripherally acting histamine H1 receptor antagonist and a selective, brain-penetrating antagonist for histamine H2 and H3 receptors, respectively. The metoprine action was mimicked by SKF 91488 (100 μg/animal, i.c.v.), another HMT inhibitor, and the action of SKF 91488 was also blocked by pyrilamine. The frequency of the expression of METH-induced total stereotypic patterns was unchanged after metoprine pretreatment. Mice pretreated with metoprine displayed no anxiety-like behavior in the elevated plus maze test. These results suggest that brain histamine, increased by agents such as metoprine and SKF 91488, binds to histamine H1 receptors in the brain, resulting in the modulation of dopaminergic transmission associated with stereotyped behavioral patterns induced by METH.

Section snippets

Subjects

Male ICR mice (8–9 weeks old; Japan SLC, Shizuoka, Japan) were housed in groups of eight (cage size, 37×22×15 cm) in a temperature- (22±2 °C) and humidity- (50±10%) controlled environment under a 12-h light/dark cycle (lights on at 07:00 h) with food and water available ad libitum except during the observations of stereotyped behavior and measurements of locomotor activity (see below). Animal handling and care were conducted according to the Guide for the Care and Use of Laboratory Animals (7th

Stereotypic scores after the administration of METH and Mtp in combination to mice

The stereotypic scores reached a plateau 20 min after a single administration of 10 mg/kg METH, which lasted until 1 h after administration (mixed factor ANOVA followed by Tukey-Kramer test, METH challenge effect, F(1,1040)=5135, P<0.001) (Fig. 1). The expression time-course of stereotypic scores induced by METH was not affected by pretreatment with various doses of Mtp (Mtp pretreatment×METH challenge interaction effect, F(3,1040)=0.639, P=0.5919). Pretreatment with Mtp per se did not

Differential regulation of METH-induced distinguishable behavioral patterns by HMT enzyme activity

The main finding of the present study is that pretreatment with Mtp, a selective inhibitor of HMT, significantly influenced the METH-induced stereotyped behavior by causing a transition from B to S in a dose-dependent manner (Fig. 2B). Mtp action was completely abolished by pyrilamine and ketotifen, selective, centrally acting histamine H1 receptor antagonists, but not fexofenadine, a peripherally acting H1 receptor antagonist (Fig. 3B and Table 1), suggesting that Mtp exerts its effects

Conclusion

Overall, the data presented here suggested that exogenously administered agents, such as Mtp and SKF 91488, that are able to increase brain histamine level enhanced the expression of METH-induced sniffing behavior via histamine H1 receptors. This is the first report to demonstrate histaminergic regulation of the expression patterns of stereotyped behavior induced by METH.

Acknowledgments

Metoprine was generously donated by GlaxoSmithKline (Stevenage, UK). NK was supported by a Grant-in-Aid for Researchers, Hyogo College of Medicine. The authors thank Mr. T. Nakajima of Joint-Use Research Facilities, Hyogo College of Medicine, for constructing the acrylic test boxes and elevated plus maze.

References (51)

  • E. Kasziba et al.

    Simultaneous determination of histidine-containing peptides, histamine, methylhistamine and histidine by high-performance liquid chromatography

    J Chromatogr

    (1988)
  • J. Kitanaka et al.

    2-Phenylethylamine in combination with l-deprenyl lowers the striatal level of dopamine and prolongs the duration of the stereotypy in mice

    Pharmacol Biochem Behav

    (2005)
  • N. Kitanaka et al.

    Behavioral sensitization and alteration in monoamine metabolism in mice after single versus repeated methamphetamine administration

    Eur J Pharmacol

    (2003)
  • T.M. Korotkova et al.

    Histamine excites GABAergic cells in the rat substantia nigra and ventral tegmental area in vitro

    Neurosci Lett

    (2002)
  • P. Malmberg-Aiello et al.

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

    Pharmacol Biochem Behav

    (2002)
  • T. Nishikawa et al.

    Behavioral sensitization and relative hyperresponsiveness of striatal and limbic dopaminergic neurons after repeated methamphetamine treatment

    Eur J Pharmacol

    (1983)
  • J.M. Palacios et al.

    The distribution of histamine H1-receptors in the rat brain: an autoradiographic study

    Neuroscience

    (1981)
  • P. Panula et al.

    Histamine-immunoreactive nerve fibers in the rat brain

    Neuroscience

    (1989)
  • A. Ramos et al.

    A multiple-test study of anxiety-related behaviours in six inbred rat strains

    Behav Brain Res

    (1997)
  • T.E. Robinson et al.

    Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis

    Brain Res Rev

    (1986)
  • N. Sakai et al.

    Effects of (S)-α-fluoromethylhistamine and metoprine on locomotor activity and brain histamine content in mice

    Life Sci

    (1992)
  • E.M. Schulz et al.

    Distinctions between stereotyped sniffing and licking in rats with methamphetamine and apomorphine

    Pharmacol Biochem Behav

    (1981)
  • J.M. Arrang et al.

    Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor

    Nature

    (1983)
  • J.J. Balsara et al.

    Effect of drugs influencing central serotonergic mechanisms on methamphetamine-induced stereotyped behavior in the rat

    Psychopharmacology (Berl)

    (1979)
  • K.E. Barke et al.

    Characterization of basal and morphine-induced histamine release in the rat periaqueductal gray

    J Neurochem

    (1994)
  • Cited by (0)

    1

    These authors contributed equally to this work.

    View full text