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  2. In vivo evaluation of effects of histamine H3 receptor antagonists on methamphetamine-induced hyperlocomotion in mice

In vivo evaluation of effects of histamine H3 receptor antagonists on methamphetamine-induced hyperlocomotion in mice

  • Brain Res. 2020 Aug 1;1740:146873. doi: 10.1016/j.brainres.2020.146873.
Junichi Kitanaka 1 Nobue Kitanaka 2 F Scott Hall 3 Yukie Amatsu 2 Kotaku Hashimoto 2 Erina Hisatomi 2 Eri Kitao 2 Mari Mimura 2 Miyu Nakamura 2 Rena Ozawa 2 Miho Sato 2 Kenta Tagami 2 George R Uhl 4 Motohiko Takemura 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan. Electronic address: kitanaka-hyg@umin.net.
  • 2 Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
  • 3 Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.
  • 4 Neurology and Research Services, New Mexico VA Healthcare System, Albuquerque, NM 87108, USA; Departments of Neurology, Neuroscience, Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USA.
Abstract

A single administration with METH (3 mg/kg) induced a hyperlocomotion in male ICR mice. Pretreatment of mice with pitolisant, a histamine H3 receptor antagonist (5 and 10 mg/kg), for 30 min showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle (saline)-pretreated subjects. Pretreatment of mice with the histamine H3 receptor antagonists JNJ-10181457 (5 and 10 mg/kg) or conessine (20 mg/kg), also showed similar inhibitory effects on METH-induced hyperlocomotion, similar to pitolisant. No significant change in locomotion was observed in mice pretreated with pitolisant, JNJ-10181457, or conessine alone. The pitolisant (10 mg/kg) action on METH-induced hyperlocomotion was completely abolished by the histamine H1 receptor antagonist pyrilamine (10 mg/kg), but not by the peripherally acting histamine H1 receptor antagonist fexofenadine (20 mg/kg), the brain-penetrating histamine H2 receptor antagonist zolantidine (10 mg/kg), or the brain-penetrating histamine H4 receptor antagonist JNJ-7777120 (40 mg/kg). Pretreatment with a histamine H3 receptor agonist immepip (10 mg/kg) augmented METH--induced behavior, including hyperlocomotion and stereotyped biting, and combined pretreatment with pitolisant (10 mg/kg) significantly attenuated stereotyped biting. These observations suggest that pretreatment with histamine H3 receptor antagonists attenuate METH-induced hyperlocomotion via releasing histamine after blocking H3 receptors, which then bind to the post-synaptic Histamine Receptor H1 (but not H2 or H4). It is likely that activation of brain histamine systems may be a good strategy for the development of agents, which treat METH abuse and dependence.

Keywords

Conessine; Histamine H(3) receptor antagonist; Hyperlocomotion; JNJ-10181457; Methamphetamine; Pitolisant.

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