title: Influence of the novel histamine H₃ receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.
abstract: BACKGROUND
  Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R).
  
  
  OBJECTIVE
  In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated.
  
  
  METHODS
  Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions. EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured.
  
  
  RESULTS
  Following administration of the H3R antagonist (2.5, 5, and 10 mg/kg, i.p.), there was a significant dose-dependent decrease in alcohol consumption and preference. Importantly, vehicle- and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes. More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion. This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs.
  
  
  CONCLUSIONS
  Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism. Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction.
authors.affiliation: Department of Anatomy, United Arab Emirates University, Tawam Medical Campus, PO Box 17666, Al Ain, United Arab Emirates. amine.bahi@uaeu.ac.ae
authors.forename: Amine
authors.initials: A
authors.lastname: Bahi
authors.forename: Bassem
authors.initials: B
authors.lastname: Sadek
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Schwed
authors.forename: Miriam
authors.initials: M
authors.lastname: Walter
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011803:Quinine / Q000008:administration & dosage; D012054:Reinforcement, Psychology; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage
chemical_list: D054828:Histamine H3 Antagonists; D000431:Ethanol; D011803:Quinine; D012439:Saccharin