ORIGINAL INVESTIGATION Influence of the novel histamine H 3 receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice Amine Bahi & Bassem Sadek & Stephan J. Schwed & Miriam Walter & Holger Stark Received: 7 November 2012 / Accepted: 31 January 2013 / Published online: 9 March 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Rationale 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 par- ticular through histamine H 3 receptors (H 3 R). Objective In the present study, the effects of systemic injec- tion of the newly synthesized H 3 R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned re- ward 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 H 3 R 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 con- centration 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 H 3 R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs. Conclusion 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 H 3 R modulation in the pharma- cotherapy of EtOH addiction. Keywords Alcohol . Conditioned place preference . Ethanol . Histamine H 3 receptor . Histamine . R-(alpha)-methyl- Histamine (RAMH) . ST1283 . Two-bottle choice Abbreviations BEC Blood ethanol concentration CPP Conditioned place preference EtOH Ethanol H 3 R Histamine H 3 receptor NAcc Nucleus accumbens RAMH R-(alpha)-methyl-histamine VTA Ventral tegmental area Introduction Alcoholism and ethanol (EtOH) abuse is a chronic re- lapsing disorder, but the development of efficient thera- pies has been largely disregarded by pharmaceutical companies. Although the molecular mechanisms in- volved in EtOH addiction are not fully understood, it is well established that neural circuits involving neuro- transmitters (e.g., histamine) are implicated in alcohol Amine Bahi and Bassem Sadek contributed equally to this work. A. Bahi (*) Department of Anatomy, United Arab Emirates University, Tawam Medical Campus, PO Box 17666, Al Ain, United Arab Emirates e-mail: amine.bahi@uaeu.ac.ae B. Sadek Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates S. J. Schwed : M. Walter : H. Stark Institut für Pharmazeutische Chemie, Biozentrum, Johann Wolfgang Goethe University, Max-von-Laue-Str. 9, 60439 Frankfurt, Germany Psychopharmacology (2013) 228:85–95 DOI 10.1007/s00213-013-3019-7