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

• Published in: Brain research Vol. 1740; p. 146873
• Main Authors: Kitanaka, Junichi, Kitanaka, Nobue, Hall, F. Scott, Amatsu, Yukie, Hashimoto, Kotaku, Hisatomi, Erina, Kitao, Eri, Mimura, Mari, Nakamura, Miyu, Ozawa, Rena, Sato, Miho, Tagami, Kenta, Uhl, George R., Takemura, Motohiko
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2020
• Subjects: Conessine; Histamine H3 receptor antagonist; Hyperlocomotion; JNJ-10181457; Methamphetamine; Pitolisant; Histamine H3 receptor antagonist; Conessine; DMSO; Methamphetamine; METH; i.p; JNJ-10181457; Pitolisant; Hyperlocomotion; HMT
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2020.146873

•Histamine H3 receptor antagonists attenuated METH-induced hyperlocomotion in mice.•H1 antagonists inhibited effect of H3 antagonists on METH-induced behavior.•H3 antagonists may be considered as candidates for treatment of METH actions. 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.