title: Histamine H3 receptor antagonist JNJ-39220675 modulates locomotor responses but not place conditioning by dopaminergic drugs.
abstract: BACKGROUND
  Brain histaminergic system is involved in the regulation of the dopaminergic circuitry. The role of histamine H3 receptor (H3R) in behaviors linked to amphetamine addiction and other behaviors induced by dopaminergic compounds has remained unclear.
  
  
  OBJECTIVE
  Our aim was to study whether H3R antagonist JNJ-39220675 inhibits amphetamine-induced stimulation and reward. The effects of JNJ-39220675 on dopamine D2-like receptor (D2R-like) agonist quinpirole-induced behaviors were also investigated in order to clarify whether the possible effects of H3R antagonists are D2R-like dependent.
  
  
  METHODS
  The effects of JNJ-39220675 on amphetamine and quinpirole-induced behavioral responses in mice were studied assessing the locomotor activation after both acute and repeated administrations of amphetamine and quinpirole. The place conditioning paradigm was also used as a measure of reward or aversion.
  
  
  RESULTS
  JNJ-39220675 inhibited amphetamine-induced stimulation acutely but not after repeated administrations. Amphetamine (2 mg/kg) induced conditioned place preference that was not affected by either of the tested doses of JNJ-39220675 (1 and 10 mg/kg). Quinpirole (0.5 mg/kg) induced conditioned place aversion to which the pretreatment by JNJ-39220675 (10 mg/kg) had no effect. In repeated administration, JNJ-39220675 did, however, inhibit quinpirole-induced tolerance to hypokinesia.
  
  
  CONCLUSIONS
  Our results show that although H3R antagonists inhibit ethanol reward, they may not possess the same ability on psychostimulants, such as amphetamine. However, if H3R antagonists will become clinically available, it is of importance that these compounds potentiate neither the rewarding nor aversive effects of other drugs.
authors.affiliation: Neuroscience Center and Institute of Biomedicine/Anatomy, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), 00014, Helsinki, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Vanhanen
authors.forename: Marja
authors.initials: M
authors.lastname: Kinnunen
authors.forename: Saara
authors.initials: S
authors.lastname: Nuutinen
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001381:Azepines / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D018100:Receptors, Histamine H3 / Q000502:physiology*; D012201:Reward
chemical_list: C559587:(4-cyclobutyl-(1,4)diazepan-1-yl)-(6-(4-fluorophenoxy)pyridin-3-yl)methanone; D001381:Azepines; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D018491:Dopamine Agonists; D054828:Histamine H3 Antagonists; D011725:Pyridines; D018100:Receptors, Histamine H3; D019257:Quinpirole; D000431:Ethanol; D000661:Amphetamine