Previous studies have demonstrated that the histamine H3 receptor inverse 
agonist thioperamide potentiates the stimulant and rewarding effects of cocaine. 
However, these potentiating effects of thioperamide do not necessarily result 
from H3 receptor blockade since thioperamide is an imidazole-based compound 
capable of enhancing plasma cocaine concentrations by blocking cytochrome P450 
activity. In contrast, Pitolisant is a non-imidazole H3 receptor inverse agonist 
that has already been tested in clinical trials but it remains to be determined 
whether this compound also potentiates the behavioral effects of cocaine. The 
present study tested the effects of Pitolisant on locomotion, on cocaine-induced 
hyperactivity and on the development of conditioned place preference induced by 
cocaine (2 and 8mg/kg, i.p.) in male C57BL/6J mice. Pitolisant was injected 
30min before each cocaine-pairing session. Locomotion recorded on the first 
cocaine-pairing session was used to test the effects of Pitolisant on the 
locomotor effects of cocaine. Our results show that doses of Pitolisant higher 
than 10mg/kg depressed locomotion. When injected alone at doses that did not 
affect locomotion, Pitolisant (2.5-10mg/kg, i.p.) had no rewarding properties in 
the place conditioning technique. Additionally, Pitolisant did not significantly 
alter cocaine-induced hyperactivity and cocaine-induced conditioned place 
preference. Taken together, our study indicates that Pitolisant has no addictive 
properties alone. Moreover, this compound does not significantly affect the 
stimulant and rewarding effects of cocaine. These results add further evidence 
to support the hypothesis that a pharmacokinetic interaction is involved in the 
ability of thioperamide to potentiate cocaine's psychomotor effects.