A single administration with METH induced a hyperlocomotion in mice. Pretreatment of mice with pitolisant, a histamine H3 receptor inverse agonist, for 30 min showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle-pretreated subjects, in a dose-dependent manner. Pretreatment of mice with JNJ-10181457, another H3 receptor inverse agonist, showed a similar inhibitory effect on METH-induced hyperlocomotion. No significant change in locomotion was observed in mice pretreated with pitolisant or JNJ-10181457 alone. Pretreatment with pitolisant prior to a high-dose METH significantly decreased the intensity of stereotyped behaviors and increased its latency to onset in a dose-dependent manner. The pitolisant action on METH-induced hyperlocomotion was completely abolished by a H1 receptor antagonist pyrilamine, but not by H2 receptor antagonist zolantidine. These observations suggest that pretreatment with pitolisant attenuates METH-induced hyperlocomotion via histamine receptors 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.

To: 要旨(抄録)