In vivo evaluation of effects of various histamine H3 receptor inverse agonists on methamphetamine-induced hyperlocomotion and stereotyped behavior in mice

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society p. 1-P-025
• Main Authors: Kitanaka, Nobue, Kitanaka, Junichi, Amatsu, Yukie, Ozawa, Rena, Sato, Miho, Hashimoto, Kotaku, Hisatomi, Erina, Kitao, Eri, Mimura, Mari, Nakamura, Miyu, Tagami, Kenta, Tanaka, Koh-ichi, Igarashi, Kento, Tomita, Kazuo, Sato, Tomoaki, Nishiyama, Nobuyoshi, Hall, F. Scott, Uhl, George R., Takemura, Motohiko
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Pharmacological Society 2020
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.93.0_1-P-025

Pretreatment of mice with pitolisant, a histamine H3 receptor antagonist, showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle (saline)-pretreated subjects. The pitolisant action on METH-induced hyperlocomotion was completely abolished by a histamine H1 receptor antagonist pyrilamine resulting in hyperlocomotion, but not by a peripherally acting histamine H1 receptor antagonist fexofenadine, a brain-penetrating histamine H2 receptor antagonist zolantidine, or a brain-penetrating histamine H4 receptor antagonist JNJ-7777120. Pretreatment with a histamine H3 receptor agonist immepip rather augmented METH (3 mg/kg)-induced behavioral abnormalities from hyperlocomotion to stereotyped biting, and, combined pretreatment of pitolisant with immepip significantly attenuated the stereotyped behaviors. Pretreatment with JNJ-10181457 or conessine, other histamine H3 receptor antagonists, showed inhibitory effects on METH-induced hyperlocomotion similar to that of pitolisant. No significant change in locomotion was observed in mice pretreated with pitolisant, JNJ-10181457, or conessine alone. Pretreatment with pitolisant prior to a high-dose METH (10 mg/kg) significantly decreased the intensity of stereotyped behaviors and increased its latency to onset in a dose-dependent manner. JNJ-1018145, but not conessine, mimicked the inhibitory action on METH-induced stereotyped behavior.