title: Action of Pitolisant on the stimulant and rewarding effects of cocaine in mice.
abstract: 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.
authors: Département de Psychologie, Cognition et Comportement, Université de Liège, Boulevard du Rectorat, 5/B32, Liège, Belgium; Unité de Psychoneuroendocrinologie, Département des sciences cliniques, Université de Liège, Avenue de l'Hôpital, 13/B35, B-4000 Liège, Belgium. Electronic address: christian.brabant@ulg.ac.be.
authors: Christian
authors: C
authors: Brabant
authors: Département de Psychologie, Cognition et Comportement, Université de Liège, Boulevard du Rectorat, 5/B32, Liège, Belgium.
authors: Yana
authors: Y
authors: Charlier
authors: Département de Psychologie, Cognition et Comportement, Université de Liège, Boulevard du Rectorat, 5/B32, Liège, Belgium.
authors: Maria Elisa Serrano
authors: MES
authors: Navacerrada
authors: Département de Psychologie, Cognition et Comportement, Université de Liège, Boulevard du Rectorat, 5/B32, Liège, Belgium.
authors: Livia
authors: L
authors: Alleva
authors: Département de Psychologie, Cognition et Comportement, Université de Liège, Boulevard du Rectorat, 5/B32, Liège, Belgium.
authors: Ezio
authors: E
authors: Tirelli
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology*; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D010880:Piperidines; C516975:pitolisant; D003042:Cocaine
keywords: Cocaine; Conditioned place preference; Histamine H3 receptor; Locomotion; Pitolisant; Reward