[Updated on Apr. 18] Integration of CiNii Articles into CiNii Research

Histamine H<sub>3</sub> receptor inverse agonists alleviate methamphetamine-induced behavioral abnormalities in mice via histamine H<sub>1</sub> receptors

  • Kitanaka Nobue
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Kitanaka Junichi
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Amatsu Yukie
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Ozawa Rena
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Sato Miho
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Hashimoto Kotaku
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Hisatomi Erina
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Kitao Eri
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Mimura Mari
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Nakamura Miyu
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Tagami Kenta
    Department of Pharmacology, Hyogo College of Medicine, Japan
  • Tanaka Koh-ichi
    Division of Pharmacology, Department of Pharmacology, School of Pharmacy, Hyogo University of Health Sciences, Japan
  • Tomita Kazuo
    Division of Pharmacology, Department of Pharmacology, School of Pharmacy, Hyogo University of Health Sciences, Japan Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
  • Tsukahara Takao
    Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
  • Sato Tomoaki
    Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
  • Nishiyama Nobuyuki
    Division of Pharmacology, Department of Pharmacology, School of Pharmacy, Hyogo University of Health Sciences, Japan
  • Hall F. Scott
    Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, USA
  • Uhl George R.
    New Mexico VA Healthcare System/BRINM, USA
  • Takemura Motohiko
    Department of Pharmacology, Hyogo College of Medicine, Japan

Abstract

<p>Background: Due to its highly addictive properties, and the adverse consequences associated with acute and chronic use of methamphetamine (METH), effective treatments for METH dependence are needed. Unfortunately, various attempts at pharmacotherapy trials have yielded unpromising and inconsistent results using medications developed to date. Several novel alternative approaches have been a matter of intense investigation more recently, including dopamine D3 receptor antagonists and partial agonists, and manipulations of brain histamine systems. The later possibility is addressed in this presentation.</p><p>Methods: We investigated whether pretreatment with histamine H3 receptor inverse agonists such as pitolisant and JNJ-10181457 affected METH-induced hyperlocomotion and stereotypy in male ICR mice. Locomotor activity was measured by Animex Auto. Quantification of the incidence of stereotyped behavior was made by trained observers blinded to the experimental conditions.</p><p>Results: A single administration with METH (3 mg/kg, i.p.) induced hyperlocomotion in mice. Pretreatment of mice with pitolisant or JNJ-10181457 showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle- (saline) pretreated subjects. No significant change in locomotion was observed in mice pretreated with H3 receptor inverse agonists alone. Pretreatment with pitolisant or JNJ-10181457 prior to a high-dose METH (10 mg/kg, i.p.) significantly decreased the intensity of stereotyped behaviors and increased its latency of onset in a dose-dependent manner. The pitolisant action on METH-induced hyperlocomotion was completely abolished by a histamine H1 receptor antagonist pyrilamine, but not by a brain-penetrating histamine H2 receptor antagonist zolantidine.</p><p>Conclusions: These observations suggest that pretreatment with H3 receptor inverse agonists attenuate METH-induced behavioral abnormalities via the histamine receptor subtype H1, but not H2, and support the idea that activation of brain histamine systems may be a good strategy for the development of agents which treat METH abuse and dependence.</p>

Journal

Details

Report a problem

Back to top